</head> <body>Dendritic Cell Map Dendritic cells (DC) are innate immune cells that can have both myeloid and lymphoid origin. The main marker for mature dendritic cells is CD83+. Immature dendritic cells express among others HLA-DR, CD80, CD86, CD1a, CD40, CD14, CD11c, CD209, ILT3. 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</extension> <glyph class="compartment" id="c6_ca6"> <label text="Phagosome/Endosome/Lysosome"> <bbox w="140.0" h="10.0" x="2447.0" y="2438.5"/> </label> <bbox w="1210.0" h="1045.0" x="1930.0" y="1440.0"/> </glyph> <glyph class="compartment" id="c9_ca9"> <label text="Phagosome/Endosome/Lysosome_Membrane"> <bbox w="185.0" h="10.0" x="2454.5" y="2608.3555"/> </label> <bbox w="1450.0" h="1330.0" x="1850.0" y="1315.0"/> </glyph> <glyph class="compartment" id="c7_ca7"> <label text="Endoplasmic Reticulum"> <bbox w="110.0" h="10.0" x="4427.079" y="2950.3804"/> </label> <bbox w="1485.0" h="441.25" x="3870.0" y="2548.75"/> </glyph> <glyph class="compartment" id="c10_ca10"> <label text="Endoplasmic Reticulum_Membrane"> <bbox w="155.0" h="10.0" x="4556.9976" y="3088.1562"/> </label> <bbox w="1850.0" h="810.0" x="3690.0" y="2343.75"/> </glyph> <glyph class="compartment" id="c2_ca2"> <label text="Cytosol"> <bbox w="40.0" h="10.0" x="3901.0" y="2309.75"/> </label> <bbox w="5780.0" h="2707.5" x="925.0" y="651.25"/> </glyph> <glyph class="compartment" id="c1_ca1"> <label text="Membrane"> <bbox w="45.0" h="10.0" x="1873.0715" y="804.5577"/> </label> <bbox w="7100.0" h="3548.75" x="225.0" y="270.0"/> </glyph> <glyph class="macromolecule" id="s778_sa2" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF receptor superfamily member 1A HUGO:TNFRSF1A hgnc_id:HGNC:11916 HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:21133840, PMID:24378531 TNF acts through two transmembrane receptors: TNF receptor 1 (TNFR1), also known as p55 or p60, and TNF receptor 2 (TNFR2), also known as p75 or p80. Macrophages are reported to express both receptors. PMID:8642347 Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling. TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was minimal, with citers leveling off 6 d after immunization. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNFR1*"/> <bbox w="80.0" h="50.0" x="5125.0" y="475.0"/> <glyph class="unit of information" id="_9487713e-55e0-45e0-88e4-921654e07ea4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5142.5" y="470.0"/> </glyph> </glyph> <glyph class="complex" id="s815_csa2" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:FADD:RIPK1:TNF:TNFR1*:TRADD:TRAF2 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:21133840, PMID:24378531 TNF acts through two transmembrane receptors: TNF receptor 1 (TNFR1), also known as p55 or p60, and TNF receptor 2 (TNFR2), also known as p75 or p80. Macrophages are reported to express both receptors. PMID:21232017, PMID:21133840, PMID:17301840 cIAP1 and cIAP2 modify RIP1, TRAF2 and themselves with K63-linked ubiquitin chains. This creates docking sites for the LUBAC complex, an E3 ligase capable of forming linear polyubiquitin chains. The LUBAC complex ubiquitinates NEMO, a subunit of the IKK complex, which by help of its IKK2 subunit also interacts with TRADD-bound TRAF2. In parallel, the TAK1-TAB 2 complex interacts with K63-ubiquitin modiﬁed RIP1 by use of the K63-ubiquitin binding TAB 2 subunit. TAK1 become activated and then phosphorylates and activates IKK2 which in turn now phosphorylates IjBa, marking it for K48-ubiquitination and proteasomal degradation. PMID:11438547, PMID:24378531 Both TNFR1 and TNFR2 signaling pathways induce classical NFkB activation via IKBa degradation. Both TNFR1 and TNFR2 signaling pathways induce JNK activation and downstrean c-jun phosphorylation. Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNFR1"/> <bbox w="210.0" h="180.0" x="5175.0" y="600.0"/> <glyph class="macromolecule" id="s832_sa11"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: receptor interacting serine/threonine kinase 1 HUGO:RIPK1 hgnc_id:HGNC:10019 HGNC:10019 ENTREZ:8737 UNIPROT:Q13546 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:21232017, PMID:21133840, PMID:18641653 TNF induces TRADD-dependent and RIPK1-dependent recruitment of TRAF2 to TNFR1. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RIPK1"/> <bbox w="80.0" h="40.0" x="5190.0" y="710.0"/> <glyph class="state variable" id="_de4a686e-e9c0-44e8-9260-8a64743ac916"> <state value="Ub" variable=""/> <bbox w="20.0" h="10.0" x="5260.0" y="725.4336"/> </glyph> </glyph> <glyph class="macromolecule" id="s831_sa12"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TNFRSF1A associated via death domain HUGO:TRADD hgnc_id:HGNC:12030 HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14730360 TRADD is an adaptor molecule important for transducing signals from TNFR1. After binding of TNF, TRADD is recruited to TNFR1 and interacts with the cytoplasmic death domain region of TNFR1 through homotypic interactions. The TNFR1-TRADD complex serves as scaffolding for the recruitment of other signaling molecules that mediate the downstream actions of TNF. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRADD"/> <bbox w="80.0" h="40.0" x="5190.0" y="660.0"/> </glyph> <glyph class="macromolecule" id="s833_sa13"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TNF receptor associated factor 2 HUGO:TRAF2 hgnc_id:HGNC:12032 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:21232017, PMID:21133840, PMID:18641653 TNF induces TRADD-dependent and RIPK1-dependent recruitment of TRAF2 to TNFR1. TNFR2 interacts with TRAF2 and TRAF1. PMID:24378531 TNF via TNFR2 induces TRAF2 degradation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAF2"/> <bbox w="80.0" h="40.0" x="5190.0" y="610.0"/> <glyph class="state variable" id="_fbe5d58a-e0b3-409f-b82f-a1b334f5bd83"> <state value="Ub" variable=""/> <bbox w="20.0" h="10.0" x="5260.0" y="623.6673"/> </glyph> </glyph> <glyph class="macromolecule" id="s830_sa14"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: tumor necrosis factor HUGO:TNF hgnc_id:HGNC:11892 HGNC:11892 ENTREZ:7124 UNIPROT:P01375 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12391186 Maturation of monocyte-derived DCs was induced by TNF-α The surface levels of MHC class II increased markedly after TNF-α stimulation on CD83+ DC In contrast to the striking increase in surface expression of MHC class II, the cell surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:12928370 TNF, but not IL-1, induce monocytes to become DCs despite the presence of fibroblasts. TNF converts activated monocytes/early Mφ into DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNF"/> <bbox w="80.0" h="40.0" x="5285.0" y="610.0"/> </glyph> <glyph class="macromolecule" id="s829_sa15"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TNF receptor superfamily member 1A HUGO:TNFRSF1A hgnc_id:HGNC:11916 HGNC:11916 ENTREZ:7132 UNIPROT:P19438 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:21133840, PMID:24378531 TNF acts through two transmembrane receptors: TNF receptor 1 (TNFR1), also known as p55 or p60, and TNF receptor 2 (TNFR2), also known as p75 or p80. Macrophages are reported to express both receptors. PMID:8642347 Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling. TNFR1-/- and TNFR2-/- mice displayed a normal spleen microarchitecture and mounted an IgM and IgG antibody response to SRBC. However, the IgG production in TNFR1-/- mice was minimal, with citers leveling off 6 d after immunization. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNFR1*"/> <bbox w="80.0" h="50.0" x="5285.0" y="655.0"/> <glyph class="unit of information" id="_5995866a-0871-48ce-86e5-c53f2b8867b6"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5302.5" y="650.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s828_sa16"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Fas associated via death domain HUGO:FADD hgnc_id:HGNC:3573 HGNC:3573 ENTREZ:8772 UNIPROT:Q13158 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FADD"/> <bbox w="80.0" h="40.0" x="5290.0" y="710.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s686_sa21" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: toll like receptor 4 HUGO:TLR4 hgnc_id:HGNC:11850 HGNC:11850 ENTREZ:7099 UNIPROT:O00206 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. PMID:16489357, PMID:17704786, PMID:23811849 TLR4 signaling induces antigens for presentation, by DC in tumors. syngeneic WT, Trif-/-, Tlr1-/-, Tlr2-/-, Tlr3-/-, Tlr5-/-, Tlr6-/-, Tlr7-/- or Tlr9-/- DCs could present antigen from dying tumor cells, Tlr4-/- and Myd88-/- DCs were defective in this function PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. PMID:11477091,PMID:14607893 Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10, which is also associated to Th1 responses. In contrast, TLR2 stimulation failed to induce IL-12 p70 and interferon-gamma inducible protein (IP)-10 but resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development. TLR2 stimulation also resulted in preferential induction of IL-8 and p19/IL-23. Thus, Escherichia coli LPS and flagellin, which trigger TLR4 and TLR5, respectively, instruct DCs to stimulate Th1 responses via IL-12p70 production, which depends on the phosphorylation of p38 and c-Jun N-terminal kinase 1/2. In contrast, the TLR2 agonist, Pam3cys, and the Th2 stimulus, schistosome egg Ags: 1) barely induce IL-12p70; 2) stimulate sustained duration and magnitude of extracellular signal-regulated kinase 1/2 phosphorylation, which results in stabilization of the transcription factor c-Fos, a suppressor of IL-12; and 3) yield a Th2 bias. Thus, distinct TLR agonists differentially modulate extracellular signal-regulated kinase signaling, c-Fos activity, and cytokine responses in DCs to stimulate different Th responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TLR4"/> <bbox w="80.0" h="50.0" x="5635.0" y="575.0"/> <glyph class="unit of information" id="_f77d7ee1-24b2-42b5-bc60-71ed40fa160e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5652.5" y="570.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s690_sa22" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TIR domain containing adaptor protein HUGO:TIRAP hgnc_id:HGNC:17192 HGNC:17192 ENTREZ:114609 UNIPROT:P58753 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TIRAP"/> <bbox w="80.0" h="40.0" x="5565.0" y="740.0"/> </glyph> <glyph class="macromolecule" id="s691_sa23" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: lymphocyte antigen 96 HUGO:LY96 hgnc_id:HGNC:17156 HGNC:17156 ENTREZ:23643 UNIPROT:Q9Y6Y9 Identifiers_end Maps_Modules_begin: MODEULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and activates TLR4/MyD88 signaling pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II and MHC I). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LY96"/> <bbox w="80.0" h="40.0" x="5565.0" y="680.0"/> </glyph> <glyph class="macromolecule" id="s689_sa24" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: myeloid differentiation primary response 88 HUGO:MYD88 hgnc_id:HGNC:7562 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. PMID:17704786 DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MYD88"/> <bbox w="80.0" h="40.0" x="5565.0" y="790.0"/> </glyph> <glyph class="macromolecule" id="s667_sa27" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 receptor associated kinase 4 HUGO:IRAK4 hgnc_id:HGNC:17967 HGNC:17967 ENTREZ:51135 UNIPROT:Q9NWZ3 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12620219 MyD88 mediates a close interaction of the two related IRAK molecules, which is essential to allow IRAK-4 to phosphorylate IRAK-1. Phosphorylation of IRAK-1 reduces its affinity for MyD88, while increasing its affinity for TRAF6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRAK4"/> <bbox w="80.0" h="40.0" x="5255.0" y="880.0"/> </glyph> <glyph class="macromolecule" id="s668_sa28" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 receptor associated kinase 2 HUGO:IRAK2 hgnc_id:HGNC:6113 HGNC:6113 ENTREZ:3656 UNIPROT:O43187 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 MyD88 recruits members of the death domain-containing serine/threonine IL-1R-associated kinase (IRAK) family. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRAK2"/> <bbox w="80.0" h="40.0" x="5285.0" y="940.0"/> </glyph> <glyph class="complex" id="s654_csa4" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CD14:LY96:MYD88:TIRAP:TLR4 Identifiers_end Maps_Modules_begin: MODULE:DC MODEULE:MDSC Maps_Modules_end References_begin: PMID:17704786, PMID:20547845 HMGB1 interacts with TLR4/LY96(MD2) complex and is internalized with the TLR4 complex after cell surface binding. PMID:16267105 HMGB1 interacts with TLR2. TLR2/TLR4 signaling downstream of HMGB1 acts via MYD88 pathway. PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. Transfection of dominant negative MyD88 or TIRAP inhibited almost all of the HMGB1- and LPS-induced NF-κB activation. MyD88 recruits members of the death domain-containing serine/threonine IL-1R-associated kinase (IRAK) family. PMID:23508573 Signaling of HMGB1 through TLR4 in macrophages requires CD14 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s654"/> <bbox w="179.375" h="180.0" x="5715.3125" y="730.0"/> <glyph class="macromolecule" id="s706_sa29"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD14 molecule HUGO:CD14 hgnc_id:HGNC:1628 HGNC:1628 ENTREZ:929 UNIPROT:P08571 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and activates TLR4/MyD88 signaling pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II and MHC I). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD14"/> <bbox w="80.0" h="40.0" x="5724.0625" y="790.0"/> </glyph> <glyph class="macromolecule" id="s674_sa30"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TIR domain containing adaptor protein HUGO:TIRAP hgnc_id:HGNC:17192 HGNC:17192 ENTREZ:114609 UNIPROT:P58753 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TIRAP"/> <bbox w="80.0" h="40.0" x="5804.0625" y="840.0"/> </glyph> <glyph class="macromolecule" id="s673_sa31"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: myeloid differentiation primary response 88 HUGO:MYD88 hgnc_id:HGNC:7562 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. PMID:17704786 DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MYD88"/> <bbox w="80.0" h="40.0" x="5724.0625" y="840.0"/> </glyph> <glyph class="macromolecule" id="s672_sa32"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: lymphocyte antigen 96 HUGO:LY96 hgnc_id:HGNC:17156 HGNC:17156 ENTREZ:23643 UNIPROT:Q9Y6Y9 Identifiers_end Maps_Modules_begin: MODEULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and activates TLR4/MyD88 signaling pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II and MHC I). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LY96"/> <bbox w="80.0" h="40.0" x="5724.0625" y="740.0"/> </glyph> <glyph class="macromolecule" id="s4964_sa975"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: toll like receptor 4 HUGO:TLR4 hgnc_id:HGNC:11850 HGNC:11850 ENTREZ:7099 UNIPROT:O00206 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. PMID:16489357, PMID:17704786, PMID:23811849 TLR4 signaling induces antigens for presentation, by DC in tumors. syngeneic WT, Trif-/-, Tlr1-/-, Tlr2-/-, Tlr3-/-, Tlr5-/-, Tlr6-/-, Tlr7-/- or Tlr9-/- DCs could present antigen from dying tumor cells, Tlr4-/- and Myd88-/- DCs were defective in this function PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. PMID:11477091,PMID:14607893 Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10, which is also associated to Th1 responses. In contrast, TLR2 stimulation failed to induce IL-12 p70 and interferon-gamma inducible protein (IP)-10 but resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development. TLR2 stimulation also resulted in preferential induction of IL-8 and p19/IL-23. Thus, Escherichia coli LPS and flagellin, which trigger TLR4 and TLR5, respectively, instruct DCs to stimulate Th1 responses via IL-12p70 production, which depends on the phosphorylation of p38 and c-Jun N-terminal kinase 1/2. In contrast, the TLR2 agonist, Pam3cys, and the Th2 stimulus, schistosome egg Ags: 1) barely induce IL-12p70; 2) stimulate sustained duration and magnitude of extracellular signal-regulated kinase 1/2 phosphorylation, which results in stabilization of the transcription factor c-Fos, a suppressor of IL-12; and 3) yield a Th2 bias. Thus, distinct TLR agonists differentially modulate extracellular signal-regulated kinase signaling, c-Fos activity, and cytokine responses in DCs to stimulate different Th responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TLR4"/> <bbox w="80.0" h="50.0" x="5805.0" y="785.0"/> <glyph class="unit of information" id="_896cbc99-3ce6-4fd3-8a03-3d069dc4c7a5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5822.5" y="780.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s908_sa51"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 HUGO:IL15 hgnc_id:HGNC:5977 HGNC:5977 ENTREZ:3600 UNIPROT:P40933 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:7523571 Interleukin 15 (IL-15) controls both the homeostasis and the peripheral activation of natural killer (NK). Interleukin (IL) 15 activates human natural killer cells via components of the IL-2 receptor and induces cytoxic activity against tumor cells and participates in regulation of cytokine production. PMID:17398124, PMID:19913445, PMID:17459805, PMID:21307131 Dendritic cells and macrophages prime natural killer cells by trans-presenting interleukin 15. IL-15 is trans-presented on the surface of IL-15-producing cells in complex with the IL-15 receptor α chain (IL-15Rα). It results in tumoricidal activity of NK cells. PMID:14607946 DCs activate resting NK cells by expressing MHC class I-related chain A and B (MICA/B), ligands for NKG2D, in response to IFN-alpha and IL15. IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15"/> <bbox w="80.0" h="40.0" x="7035.0" y="1160.0"/> </glyph> <glyph class="complex" id="s1107_csa9" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL15RA:IL2RB:IL2RG Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1107"/> <bbox w="305.0" h="90.0" x="6862.5" y="1555.0"/> <glyph class="macromolecule" id="s1109_sa58"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 15 receptor subunit alpha HUGO:IL15RA hgnc_id:HGNC:5978 HGNC:5978 ENTREZ:3601 UNIPROT:Q13261 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15RA"/> <bbox w="80.0" h="50.0" x="6867.5" y="1570.0"/> <glyph class="unit of information" id="_e6cbb70b-a0f8-4bda-9b6d-c01c1f680f12"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6885.0" y="1565.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1110_sa59"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit beta HUGO:IL2RB hgnc_id:HGNC:6009 HGNC:6009 ENTREZ:3560 UNIPROT:P14784 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16212621 IL-2- and IL-15-induced phosphorylation of the IL-2RB chain in T cells. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RB"/> <bbox w="80.0" h="50.0" x="6967.5" y="1570.0"/> <glyph class="state variable" id="_0dc7c655-8edc-4e2f-8e3a-63227eae0bba"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6962.5" y="1590.0"/> </glyph> <glyph class="unit of information" id="_f9b714a1-4680-46af-a575-26a9612573d2"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6985.0" y="1565.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1111_sa60"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit gamma HUGO:IL2RG hgnc_id:HGNC:6010 HGNC:6010 ENTREZ:3561 UNIPROT:P31785 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RG"/> <bbox w="80.0" h="50.0" x="7067.5" y="1570.0"/> <glyph class="unit of information" id="_77aafc8e-2e12-4dce-8e9c-e21dd7106b58"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="7085.0" y="1565.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s1081_sa61" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <clone/> <bbox w="80.0" h="40.0" x="3765.0" y="360.0"/> <glyph class="state variable" id="_eb2f6c80-1b13-4cfb-9b58-adcf371a1b22"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3760.0" y="375.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1081_sa620" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <clone/> <bbox w="80.0" h="40.0" x="4855.0" y="420.0"/> <glyph class="state variable" id="_8aac1d42-4c99-41dd-b7b1-2cadd119d307"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4850.0" y="435.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s544_sa62"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 2 HUGO:CSF2 hgnc_id:HGNC:2434 HGNC:2434 ENTREZ:1437 UNIPROT:P04141 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:20805416 In differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively activated by GM-CSF And this signaling is needful for DC differentiation. PMID:15573129 For survival in vitro, myeloid DCs are dependent on GM-CSF, whereas pDCs are dependent on IL-3 and IFNA. There are some contradictory information about GM-SCF effect (activation/inhibition) in DC References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2"/> <bbox w="80.0" h="40.0" x="3680.0" y="150.0"/> </glyph> <glyph class="complex" id="s615_csa10" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CSF2:CSF2RA:CSF2RB:JAK2 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:12393492 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits PMID:20406969, PMID:24091328, PMID:11867689 GM-CSF uniquely inhibited signal transducers and activators of transcription (STAT3) and promoted STAT5 activation, probably downstream of JAK2. STAT5ab(null/null) MDSC were rendered sensitive to sunitinib in the presence of GM-CSF in vitro. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s610"/> <bbox w="182.5" h="125.0" x="3683.75" y="467.5"/> <glyph class="macromolecule" id="s614_sa63"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 2 HUGO:CSF2 hgnc_id:HGNC:2434 HGNC:2434 ENTREZ:1437 UNIPROT:P04141 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:20805416 In differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively activated by GM-CSF And this signaling is needful for DC differentiation. PMID:15573129 For survival in vitro, myeloid DCs are dependent on GM-CSF, whereas pDCs are dependent on IL-3 and IFNA. There are some contradictory information about GM-SCF effect (activation/inhibition) in DC References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2"/> <bbox w="80.0" h="40.0" x="3695.0" y="480.0"/> </glyph> <glyph class="macromolecule" id="s617_sa64"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 2 receptor beta common subunit HUGO:CSF2RB hgnc_id:HGNC:2436 HGNC:2436 ENTREZ:1439 UNIPROT:P32927 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) ( References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RB"/> <bbox w="80.0" h="50.0" x="3778.75" y="522.5"/> <glyph class="unit of information" id="_166967be-0698-4696-b534-0faf23298d29"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3796.25" y="517.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s616_sa65"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 2 receptor alpha subunit HUGO:CSF2RA hgnc_id:HGNC:2435 HGNC:2435 ENTREZ:1438 UNIPROT:P15509 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RA"/> <bbox w="80.0" h="50.0" x="3703.75" y="522.5"/> <glyph class="unit of information" id="_51f2b6a5-1c55-4075-b1e9-c7ed36f06adc"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3721.25" y="517.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1082_sa66"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <bbox w="80.0" h="40.0" x="3785.0" y="480.0"/> <glyph class="state variable" id="_84e76423-9bff-4029-a578-beceb24ddd72"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3780.0" y="495.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s610_csa11" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CSF2RA:CSF2RB Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:12393492 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s610"/> <bbox w="195.0" h="90.0" x="3517.5" y="365.0"/> <glyph class="macromolecule" id="s613_sa67"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 2 receptor beta common subunit HUGO:CSF2RB hgnc_id:HGNC:2436 HGNC:2436 ENTREZ:1439 UNIPROT:P32927 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) ( References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RB"/> <bbox w="80.0" h="50.0" x="3615.0" y="375.0"/> <glyph class="unit of information" id="_9da4081a-36d7-41ee-8454-5b86bd3d5357"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3632.5" y="370.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s612_sa68"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 2 receptor alpha subunit HUGO:CSF2RA hgnc_id:HGNC:2435 HGNC:2435 ENTREZ:1438 UNIPROT:P15509 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RA"/> <bbox w="80.0" h="50.0" x="3535.0" y="375.0"/> <glyph class="unit of information" id="_05638504-6c34-4fab-b4fd-187c0abea056"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3552.5" y="370.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s311_sa69"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 4 HUGO:IL4 hgnc_id:HGNC:6014 HGNC:6014 ENTREZ:3565 UNIPROT:P05112 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15573129, PMID:11306493 IL-4 and IL-13 reverse the inhibitory effects of either renal-cell-carcinoma-conditioned medium or IL-6 and M-CSF on the phenotypic and functional differentiation of CD34+ cells into DCs. IL-4 was found to function through rapid blockade of the expression of M-CSF and the IL-6R-transducing chain (also known as gp130), as well as a decrease in the secondary production of M-CSF, thereby preventing the loss of GM-CSF receptor -chain expression that normally occurs during the differentiation of CD34+ cell PMID:10993913 Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. IL-4 and IFN-γ together showed a strong synergism in increasing p70, while maintaining the IL-4 block of production of the antagonistic (p40)2. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4"/> <bbox w="80.0" h="40.0" x="7385.0" y="1950.0"/> </glyph> <glyph class="macromolecule" id="s240_sa70" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 2 receptor subunit gamma HUGO:IL2RG hgnc_id:HGNC:6010 HGNC:6010 ENTREZ:3561 UNIPROT:P31785 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RG"/> <bbox w="80.0" h="50.0" x="6545.0" y="1835.0"/> <glyph class="unit of information" id="_ee98e47f-5f1a-4c4e-9f67-9794a7b19a0a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6562.5" y="1830.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s122_sa71" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 4 receptor HUGO:IL4R hgnc_id:HGNC:6015 HGNC:6015 ENTREZ:3566 UNIPROT:P24394 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4R"/> <bbox w="80.0" h="50.0" x="6455.0" y="1955.0"/> <glyph class="state variable" id="_71037247-2a17-451e-ab0f-17dba3b7bc7d"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6530.0" y="1989.3893"/> </glyph> <glyph class="unit of information" id="_1f9d274b-beea-44fe-b63c-854cef1e3d21"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6472.5" y="1950.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s387_sa72" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: tyrosine kinase 2 HUGO:TYK2 hgnc_id:HGNC:12440 HGNC:12440 ENTREZ:7297 UNIPROT:P29597 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 TYK2 is a member of the Janus kinase family. TYK2 associated with IL13RA1 participates in signal transduction. PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TYK2"/> <clone/> <bbox w="80.0" h="40.0" x="6435.0" y="2230.0"/> <glyph class="state variable" id="_8fec5b3f-55f1-4a14-9f78-ecea1c840e41"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6430.0" y="2245.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s387_sa111" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: tyrosine kinase 2 HUGO:TYK2 hgnc_id:HGNC:12440 HGNC:12440 ENTREZ:7297 UNIPROT:P29597 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 TYK2 is a member of the Janus kinase family. TYK2 associated with IL13RA1 participates in signal transduction. PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TYK2"/> <clone/> <bbox w="80.0" h="40.0" x="4325.0" y="730.0"/> <glyph class="state variable" id="_37c8353c-384a-4d10-899c-32cadb2ffacb"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4320.0" y="745.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s387_sa112" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: tyrosine kinase 2 HUGO:TYK2 hgnc_id:HGNC:12440 HGNC:12440 ENTREZ:7297 UNIPROT:P29597 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 TYK2 is a member of the Janus kinase family. TYK2 associated with IL13RA1 participates in signal transduction. PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TYK2"/> <clone/> <bbox w="80.0" h="40.0" x="4325.0" y="820.0"/> <glyph class="state variable" id="_808835f1-156c-4141-b8ca-a8248ddb8d89"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4320.0" y="835.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s10_sa74" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <clone/> <bbox w="80.0" h="40.0" x="6435.0" y="2170.0"/> <glyph class="state variable" id="_b74525e0-b2b1-44c1-8650-b09af1fa1092"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6430.0" y="2185.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s10_sa109" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <clone/> <bbox w="80.0" h="40.0" x="4215.0" y="740.0"/> <glyph class="state variable" id="_1ab343f6-cf40-481e-a930-6ca7179206bd"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4210.0" y="755.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s10_sa110" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <clone/> <bbox w="80.0" h="40.0" x="4215.0" y="830.0"/> <glyph class="state variable" id="_e43fff37-8819-4397-90bf-07b7190eb117"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4210.0" y="845.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s10_sa176" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <clone/> <bbox w="80.0" h="40.0" x="1085.0" y="1900.0"/> <glyph class="state variable" id="_410e90dc-d11e-4479-a4ea-cb5e93685b15"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1080.0" y="1915.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s10_sa631" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <clone/> <bbox w="80.0" h="40.0" x="6295.0" y="1470.0"/> <glyph class="state variable" id="_e88967dc-1e6b-4e6f-987d-04b19cb00d84"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6290.0" y="1485.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s238_sa75" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 13 receptor subunit alpha 1 HUGO:IL13RA1 hgnc_id:HGNC:5974 HGNC:5974 ENTREZ:3597 UNIPROT:P78552 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620, PMID:12223527 IL13 acts via IL4 receptor type 2, which contains two subunits IL4R and IL13RA1 PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL13RA1"/> <bbox w="80.0" h="50.0" x="6465.0" y="2355.0"/> <glyph class="state variable" id="_386aafe2-534d-40a2-8f01-a7dbae96045f"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6540.0" y="2388.7566"/> </glyph> <glyph class="unit of information" id="_c9e7aafe-7a31-42df-8ec0-cbd996440e3f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6482.5" y="2350.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s422_sa78" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 3 HUGO:JAK3 hgnc_id:HGNC:6193 HGNC:6193 ENTREZ:3718 UNIPROT:P52333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK3"/> <clone/> <bbox w="80.0" h="40.0" x="6435.0" y="2040.0"/> </glyph> <glyph class="macromolecule" id="s422_sa630" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 3 HUGO:JAK3 hgnc_id:HGNC:6193 HGNC:6193 ENTREZ:3718 UNIPROT:P52333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK3"/> <clone/> <bbox w="80.0" h="40.0" x="6275.0" y="1390.0"/> </glyph> <glyph class="macromolecule" id="s422_sa675" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 3 HUGO:JAK3 hgnc_id:HGNC:6193 HGNC:6193 ENTREZ:3718 UNIPROT:P52333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK3"/> <clone/> <bbox w="80.0" h="40.0" x="2865.0" y="790.0"/> </glyph> <glyph class="complex" id="s242_csa12" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL2RG:IL4R Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:23124025, PMID:20856220 In human monocytes, IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4Ris composed of the IL-4Ra chain and IL-13Ra1 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4_receptor_TYPE1"/> <bbox w="195.5" h="79.125" x="6797.25" y="1920.4375"/> <glyph class="macromolecule" id="s329_sa79"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 4 receptor HUGO:IL4R hgnc_id:HGNC:6015 HGNC:6015 ENTREZ:3566 UNIPROT:P24394 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4R"/> <bbox w="80.0" h="50.0" x="6892.75" y="1924.5625"/> <glyph class="state variable" id="_a967cbb0-abb4-4a65-b367-9d8a566c9cfe"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6967.75" y="1958.9518"/> </glyph> <glyph class="unit of information" id="_a75f4ceb-3622-4412-9db3-f037cbc710e0"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6910.25" y="1919.5625"/> </glyph> </glyph> <glyph class="macromolecule" id="s328_sa80"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit gamma HUGO:IL2RG hgnc_id:HGNC:6010 HGNC:6010 ENTREZ:3561 UNIPROT:P31785 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RG"/> <bbox w="80.0" h="50.0" x="6812.75" y="1924.5625"/> <glyph class="unit of information" id="_ad97d508-8b79-4592-afcd-b8851203822d"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6830.25" y="1919.5625"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s331_csa13" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL2RG:IL4:IL4R:JAK1:JAK2:JAK3 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:12244147 Enhancement of IL-12 p70 production is mediated by IL-4, but not IL-13, through IL-4R type I and depends on JAK3 and STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4_receptor_TYPE1"/> <bbox w="269.0" h="151.0" x="6710.5" y="2044.5"/> <glyph class="macromolecule" id="s421_sa81"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <bbox w="80.0" h="40.0" x="6879.5" y="2135.5"/> <glyph class="state variable" id="_e94dd86d-2765-4b1d-bc23-6097b4be4d34"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6874.5" y="2150.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s420_sa82"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="6882.0" y="2097.0"/> <glyph class="state variable" id="_c5f617b1-f24c-4bcb-9c0a-b16b4ee33fee"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6874.5" y="2112.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s381_sa83"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 3 HUGO:JAK3 hgnc_id:HGNC:6193 HGNC:6193 ENTREZ:3718 UNIPROT:P52333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK3"/> <bbox w="80.0" h="40.0" x="6881.0" y="2058.0"/> </glyph> <glyph class="macromolecule" id="s330_sa84"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 4 HUGO:IL4 hgnc_id:HGNC:6014 HGNC:6014 ENTREZ:3565 UNIPROT:P05112 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15573129, PMID:11306493 IL-4 and IL-13 reverse the inhibitory effects of either renal-cell-carcinoma-conditioned medium or IL-6 and M-CSF on the phenotypic and functional differentiation of CD34+ cells into DCs. IL-4 was found to function through rapid blockade of the expression of M-CSF and the IL-6R-transducing chain (also known as gp130), as well as a decrease in the secondary production of M-CSF, thereby preventing the loss of GM-CSF receptor -chain expression that normally occurs during the differentiation of CD34+ cell PMID:10993913 Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. IL-4 and IFN-γ together showed a strong synergism in increasing p70, while maintaining the IL-4 block of production of the antagonistic (p40)2. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4"/> <bbox w="80.0" h="40.0" x="6720.5" y="2096.0"/> </glyph> <glyph class="macromolecule" id="s333_sa85"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 4 receptor HUGO:IL4R hgnc_id:HGNC:6015 HGNC:6015 ENTREZ:3566 UNIPROT:P24394 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4R"/> <bbox w="80.0" h="50.0" x="6801.357" y="2097.6428"/> <glyph class="state variable" id="_8ca5bf67-09b2-4c8b-b2d1-017917926693"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6876.357" y="2132.032"/> </glyph> <glyph class="unit of information" id="_77c1d350-f986-42f1-99a1-6d2fc4ca1505"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6818.857" y="2092.6428"/> </glyph> </glyph> <glyph class="macromolecule" id="s332_sa86"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit gamma HUGO:IL2RG hgnc_id:HGNC:6010 HGNC:6010 ENTREZ:3561 UNIPROT:P31785 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RG"/> <bbox w="80.0" h="50.0" x="6801.357" y="2058.6428"/> <glyph class="unit of information" id="_4af0e867-3aa5-46ce-b7ec-f95b872aaf94"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6818.857" y="2053.6428"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s622_csa14" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL13RA1:IL4:IL4R:JAK1:JAK2:TYK2 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:12244147 IL-4R type II signaling downstream of IL4 andIL13 is sufficient to promote DC maturation at low doses of GM-CSF. The proportions of mature DC represented by high surface expression of MHC class II (MHC II) and CD86 as well as CD80, CD40, and CD54 (data not shown) IL-4R type II signaling acts probably via STAT6. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4/Receptor-TYPE_2"/> <bbox w="222.0" h="176.5" x="6674.0" y="2251.75"/> <glyph class="macromolecule" id="s436_sa87"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: tyrosine kinase 2 HUGO:TYK2 hgnc_id:HGNC:12440 HGNC:12440 ENTREZ:7297 UNIPROT:P29597 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 TYK2 is a member of the Janus kinase family. TYK2 associated with IL13RA1 participates in signal transduction. PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TYK2"/> <bbox w="80.0" h="40.0" x="6784.0" y="2308.25"/> <glyph class="state variable" id="_22ba706c-1f4e-40cc-b7ea-0a6b8c94ff56"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6779.0" y="2323.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s435_sa88"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="6784.0" y="2268.25"/> <glyph class="state variable" id="_9986d9d1-a320-4f5c-8274-458970e29252"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6776.5" y="2283.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s437_sa89"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <bbox w="80.0" h="40.0" x="6784.0" y="2348.25"/> <glyph class="state variable" id="_d3b214dd-95db-4d4c-8c14-8f943d34633c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6779.0" y="2363.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s431_sa90"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 4 HUGO:IL4 hgnc_id:HGNC:6014 HGNC:6014 ENTREZ:3565 UNIPROT:P05112 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15573129, PMID:11306493 IL-4 and IL-13 reverse the inhibitory effects of either renal-cell-carcinoma-conditioned medium or IL-6 and M-CSF on the phenotypic and functional differentiation of CD34+ cells into DCs. IL-4 was found to function through rapid blockade of the expression of M-CSF and the IL-6R-transducing chain (also known as gp130), as well as a decrease in the secondary production of M-CSF, thereby preventing the loss of GM-CSF receptor -chain expression that normally occurs during the differentiation of CD34+ cell PMID:10993913 Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. IL-4 and IFN-γ together showed a strong synergism in increasing p70, while maintaining the IL-4 block of production of the antagonistic (p40)2. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4"/> <bbox w="80.0" h="40.0" x="6694.0" y="2268.25"/> </glyph> <glyph class="macromolecule" id="s434_sa91"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 13 receptor subunit alpha 1 HUGO:IL13RA1 hgnc_id:HGNC:5974 HGNC:5974 ENTREZ:3597 UNIPROT:P78552 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620, PMID:12223527 IL13 acts via IL4 receptor type 2, which contains two subunits IL4R and IL13RA1 PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL13RA1"/> <bbox w="80.0" h="50.0" x="6694.0" y="2313.25"/> <glyph class="state variable" id="_cdc7c486-f404-4e69-b92f-2eb4558435dd"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6769.0" y="2347.0066"/> </glyph> <glyph class="unit of information" id="_8efa4649-dfb4-4c7f-bd2d-8ab1a032ff19"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6711.5" y="2308.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s433_sa92"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 4 receptor HUGO:IL4R hgnc_id:HGNC:6015 HGNC:6015 ENTREZ:3566 UNIPROT:P24394 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4R"/> <bbox w="80.0" h="50.0" x="6694.0" y="2353.25"/> <glyph class="state variable" id="_304d9cc6-115f-4630-b44c-a5e5adbe77e8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6769.0" y="2387.6392"/> </glyph> <glyph class="unit of information" id="_5a9d6711-2ef3-4e8c-bacc-2a4a08044176"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6711.5" y="2348.25"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s241_csa15" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL13RA1:IL4R Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:14610620, PMID:12223527 IL13 acts via IL4 receptor type 2, which contains two subunits IL4R and IL13RA1 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4/IL13_receptor- TYPE 2"/> <bbox w="170.0" h="138.25" x="6960.0" y="2280.875"/> <glyph class="macromolecule" id="s429_sa93"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 4 receptor HUGO:IL4R hgnc_id:HGNC:6015 HGNC:6015 ENTREZ:3566 UNIPROT:P24394 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4R"/> <bbox w="80.0" h="50.0" x="6995.0" y="2285.0"/> <glyph class="state variable" id="_d5f105e3-59a3-40ff-bc11-20e7e6efce44"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="7070.0" y="2319.3892"/> </glyph> <glyph class="unit of information" id="_c1ebb877-8a05-4295-9029-d681b0eb64c0"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="7012.5" y="2280.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s430_sa94"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> MODULE:DC HUGO:IL13RA1 ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 13 receptor subunit alpha 1 HUGO:IL13RA1 hgnc_id:HGNC:5974 HGNC:5974 ENTREZ:3597 UNIPROT:P78552 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620, PMID:12223527 IL13 acts via IL4 receptor type 2, which contains two subunits IL4R and IL13RA1 PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL13RA1"/> <bbox w="80.0" h="50.0" x="6995.0" y="2335.0"/> <glyph class="state variable" id="_d38b4232-e350-442a-bfdf-8a78eac4022f"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="7070.0" y="2368.7566"/> </glyph> <glyph class="unit of information" id="_f29573fe-042d-4dd6-b097-a7f6ae34d168"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="7012.5" y="2330.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s1149_sa107"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon alpha 2 HUGO:IFNA2 hgnc_id:HGNC:5423 HGNC:5423 ENTREZ:3440 UNIPROT:P01563 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors. Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines RANTES, MIP-1α, and, especially, MIP-1β . Also IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNA"/> <bbox w="80.0" h="40.0" x="4195.0" y="150.0"/> </glyph> <glyph class="macromolecule" id="s1295_sa108"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon beta 1 HUGO:IFNB1 hgnc_id:HGNC:5434 HGNC:5434 ENTREZ:3456 UNIPROT:P01574 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:14607946 DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNB"/> <bbox w="80.0" h="40.0" x="4305.0" y="150.0"/> </glyph> <glyph class="macromolecule" id="s1170_sa113" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 1 HUGO:STAT1 hgnc_id:HGNC:11362 HGNC:11362 ENTREZ:6772 UNIPROT:P42224 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:24777831, PMID:19811323 The expression of MHC Class I molecules (controlled by STAT-1 and IRF-1) was increased following IFN-γ treatment PMID:24777831 iNOS expression was induced by IFN-gamma stimulation in IL4-DC but not in IL15DC via STAT1. PMID:24777831, PMID:16056253 PIAS1 is a a transcriptional repressor of STAT1. PIAS1 expression was not detected in DCs generated with IL-4. In contrast, the basal level of PIAS1 expression was substantially elevated in IL-15 DCs. combination of PIAS1 with STAT-3 inhibition led to a partial restoration of iNOS expression, NO production, and DC tumoricidal function PMID:21930769 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. PMID:14764699 STAT1 activation is mediated by synergistic interaction between IL-4 and GM-CSF Functional maturation of DCs requires STAT1. PMID:11244049 IRF1 is a Stat1 target gene. PMID: 10811870, PMID:17617740 I IFN induces TRAIL mRNA expression and enhances apoptosis of target tumor cells . Probably via STAT1 and IFR1. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT1"/> <bbox w="80.0" h="40.0" x="4585.0" y="870.0"/> <glyph class="state variable" id="_4f8d8278-c1c5-4d31-ac23-6be779772f40"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4580.0" y="885.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1214_sa114" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 1 HUGO:STAT1 hgnc_id:HGNC:11362 HGNC:11362 ENTREZ:6772 UNIPROT:P42224 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:24777831, PMID:19811323 The expression of MHC Class I molecules (controlled by STAT-1 and IRF-1) was increased following IFN-γ treatment PMID:24777831 iNOS expression was induced by IFN-gamma stimulation in IL4-DC but not in IL15DC via STAT1. PMID:24777831, PMID:16056253 PIAS1 is a a transcriptional repressor of STAT1. PIAS1 expression was not detected in DCs generated with IL-4. In contrast, the basal level of PIAS1 expression was substantially elevated in IL-15 DCs. combination of PIAS1 with STAT-3 inhibition led to a partial restoration of iNOS expression, NO production, and DC tumoricidal function PMID:21930769 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. PMID:14764699 STAT1 activation is mediated by synergistic interaction between IL-4 and GM-CSF Functional maturation of DCs requires STAT1. PMID:11244049 IRF1 is a Stat1 target gene. PMID: 10811870, PMID:17617740 I IFN induces TRAIL mRNA expression and enhances apoptosis of target tumor cells . Probably via STAT1 and IFR1. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT1"/> <bbox w="80.0" h="40.0" x="4585.0" y="970.0"/> <glyph class="state variable" id="_ea273079-ed96-41af-9852-eb32034c7f75"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4577.5" y="985.0"/> </glyph> </glyph> <glyph class="complex" id="s1300_csa19" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IFNAR1:IFNAR2:IFNB Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1282"/> <bbox w="120.0" h="230.0" x="4415.0" y="385.0"/> <glyph class="macromolecule" id="s2368_sa117"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon alpha and beta receptor subunit 1 HUGO:IFNAR1 hgnc_id:HGNC:5432 HGNC:5432 ENTREZ:3454 UNIPROT:P17181 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:21930769 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via FNAR1 and STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNAR1"/> <bbox w="80.0" h="50.0" x="4435.0" y="470.0"/> <glyph class="unit of information" id="_26c39fa1-f8de-40d0-902c-9d94be6c56f6"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4452.5" y="465.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2372_sa118"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon alpha and beta receptor subunit 2 HUGO:IFNAR2 hgnc_id:HGNC:5433 HGNC:5433 ENTREZ:3455 UNIPROT:P48551 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNAR2"/> <bbox w="80.0" h="50.0" x="4435.0" y="525.0"/> <glyph class="unit of information" id="_88ae057e-cae0-422d-86ed-50d52ba5092c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4452.5" y="520.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1299_sa119"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon beta 1 HUGO:IFNB1 hgnc_id:HGNC:5434 HGNC:5434 ENTREZ:3456 UNIPROT:P01574 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:14607946 DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNB"/> <bbox w="80.0" h="40.0" x="4435.0" y="420.0"/> </glyph> </glyph> <glyph class="complex" id="s1286_csa18" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IFNAR1:IFNAR2 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:25333658 IFNAR−/− NK cells produce significantly less granzyme B than wild-type competitor NK cells PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1282"/> <bbox w="120.0" h="175.0" x="4265.0" y="422.5"/> <glyph class="macromolecule" id="s1287_sa115"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon alpha and beta receptor subunit 1 HUGO:IFNAR1 hgnc_id:HGNC:5432 HGNC:5432 ENTREZ:3454 UNIPROT:P17181 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:21930769 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via FNAR1 and STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNAR1"/> <bbox w="80.0" h="50.0" x="4285.0" y="452.5"/> <glyph class="unit of information" id="_1cec221e-69b4-43c1-aa1b-c6c9d5280c3b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4302.5" y="447.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1288_sa116"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon alpha and beta receptor subunit 2 HUGO:IFNAR2 hgnc_id:HGNC:5433 HGNC:5433 ENTREZ:3455 UNIPROT:P48551 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNAR2"/> <bbox w="80.0" h="50.0" x="4285.0" y="512.5"/> <glyph class="unit of information" id="_f7b944b5-b5c4-4b7e-861d-cb89464d259f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4302.5" y="507.5"/> </glyph> </glyph> </glyph> <glyph class="phenotype" id="s1_sa123"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:17948027, PMID:22437871, PMID:17204652 Dendritic Cells are critical Antigen-Presenting Cells in tumor Immunity. They present processed protein and lipid antigens to T cells via both classical (major histocompatibility complex (MHC) class I and class II) and non-classical (CD1 family) antigen-presenting molecules.When compared with other APCs, such as macrophages, DCs are extremely efficient and can elicit very low numbers of T cells to respond thus explaining their nickname of 'professional APCs'. PMID:17204652 CD8- DC demonstrates overexpression of MHC class II–associated molecules and CD8+ demonstrates expression pattern of MHC class II–associated molecules. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Antigen_presentation"/> <bbox w="460.0" h="165.0" x="4060.0" y="3942.5"/> </glyph> <glyph class="macromolecule" id="s11_sa124" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 3 HUGO:STAT3 hgnc_id:HGNC:11364 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512, PMID:23894201 ‭The binding of IL-10 to its receptor activates JAK1 Two tyrosines‭ (‬Tyr‭ ‬446‭ ‬and Tyr‭ ‬496‭) ‬of IL-10RA are phosphorylated by the JAK1,‭ ‬to which the transcription factor STAT3‭ ‬binds via its SH2‭ ‬domain and in turn becomes itself phosphorylated. In DC Tyk2 has no influence on STAT3 activation. PMID:15573129 JAK2-STAT3 pathway involeved in inhibition of DC activity. The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:24777831 STAT-3 phosphorylation was enhanced in IL-15 DCs compared to IL-4 DCs PMID:25582338 IL15 induces IFNG expression in DC via STAT3. PMID:20124100, PMID:9174615, PMID:11254683, PMID:9366401 Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10-mediated suppression. TNF and IFNG production in DC is STAT3 dependent. Probably downstream IL10. STAT3 downregulates MHC-II and CD86 surface expression downstream of IL10 and IL6, IL12, production. PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:14670306 Phosphorylation of the two isoforms of STAT3 (α and β) was detectable 15 min after stimulation with different doses of Flt3L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT3"/> <clone/> <bbox w="80.0" h="40.0" x="1315.0" y="1880.0"/> <glyph class="state variable" id="_d280150a-0502-4c07-b90b-d6341bae8b2c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1310.0" y="1894.9681"/> </glyph> </glyph> <glyph class="macromolecule" id="s11_sa634" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 3 HUGO:STAT3 hgnc_id:HGNC:11364 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512, PMID:23894201 ‭The binding of IL-10 to its receptor activates JAK1 Two tyrosines‭ (‬Tyr‭ ‬446‭ ‬and Tyr‭ ‬496‭) ‬of IL-10RA are phosphorylated by the JAK1,‭ ‬to which the transcription factor STAT3‭ ‬binds via its SH2‭ ‬domain and in turn becomes itself phosphorylated. In DC Tyk2 has no influence on STAT3 activation. PMID:15573129 JAK2-STAT3 pathway involeved in inhibition of DC activity. The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:24777831 STAT-3 phosphorylation was enhanced in IL-15 DCs compared to IL-4 DCs PMID:25582338 IL15 induces IFNG expression in DC via STAT3. PMID:20124100, PMID:9174615, PMID:11254683, PMID:9366401 Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10-mediated suppression. TNF and IFNG production in DC is STAT3 dependent. Probably downstream IL10. STAT3 downregulates MHC-II and CD86 surface expression downstream of IL10 and IL6, IL12, production. PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:14670306 Phosphorylation of the two isoforms of STAT3 (α and β) was detectable 15 min after stimulation with different doses of Flt3L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT3"/> <clone/> <bbox w="80.0" h="40.0" x="5825.0" y="1470.0"/> <glyph class="state variable" id="_81b6c78c-bd6b-4291-ac09-e5d32d7e522a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="5820.0" y="1484.9681"/> </glyph> </glyph> <glyph class="macromolecule" id="s68_sa125" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: HUGO:STAT3 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512 ‭The binding of IL-10 to its receptor activates JAK1 Two tyrosines‭ (‬Tyr‭ ‬446‭ ‬and Tyr‭ ‬496‭) ‬of IL-10RA are phosphorylated by the JAK1,‭ ‬to which the transcription factor STAT3‭ ‬binds via its SH2‭ ‬domain and in turn becomes itself phosphorylated. PMID:10347215 Only JAK1/STAT3 pathway (but not TYK) plays role in anti-inflammatory action of IL10 in macrophages. References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 3 HUGO:STAT3 hgnc_id:HGNC:11364 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512, PMID:23894201 ‭The binding of IL-10 to its receptor activates JAK1 Two tyrosines‭ (‬Tyr‭ ‬446‭ ‬and Tyr‭ ‬496‭) ‬of IL-10RA are phosphorylated by the JAK1,‭ ‬to which the transcription factor STAT3‭ ‬binds via its SH2‭ ‬domain and in turn becomes itself phosphorylated. In DC Tyk2 has no influence on STAT3 activation. PMID:15573129 JAK2-STAT3 pathway involeved in inhibition of DC activity. The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:24777831 STAT-3 phosphorylation was enhanced in IL-15 DCs compared to IL-4 DCs PMID:25582338 IL15 induces IFNG expression in DC via STAT3. PMID:20124100, PMID:9174615, PMID:11254683, PMID:9366401 Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10-mediated suppression. TNF and IFNG production in DC is STAT3 dependent. Probably downstream IL10. STAT3 downregulates MHC-II and CD86 surface expression downstream of IL10 and IL6, IL12, production. PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:14670306 Phosphorylation of the two isoforms of STAT3 (α and β) was detectable 15 min after stimulation with different doses of Flt3L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT3"/> <clone/> <bbox w="80.0" h="40.0" x="1315.0" y="1980.0"/> <glyph class="state variable" id="_7afcb702-143b-4880-a478-0a676851c97b"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1307.5" y="1994.9681"/> </glyph> </glyph> <glyph class="macromolecule" id="s68_sa635" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: HUGO:STAT3 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512 ‭The binding of IL-10 to its receptor activates JAK1 Two tyrosines‭ (‬Tyr‭ ‬446‭ ‬and Tyr‭ ‬496‭) ‬of IL-10RA are phosphorylated by the JAK1,‭ ‬to which the transcription factor STAT3‭ ‬binds via its SH2‭ ‬domain and in turn becomes itself phosphorylated. PMID:10347215 Only JAK1/STAT3 pathway (but not TYK) plays role in anti-inflammatory action of IL10 in macrophages. References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 3 HUGO:STAT3 hgnc_id:HGNC:11364 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512, PMID:23894201 ‭The binding of IL-10 to its receptor activates JAK1 Two tyrosines‭ (‬Tyr‭ ‬446‭ ‬and Tyr‭ ‬496‭) ‬of IL-10RA are phosphorylated by the JAK1,‭ ‬to which the transcription factor STAT3‭ ‬binds via its SH2‭ ‬domain and in turn becomes itself phosphorylated. In DC Tyk2 has no influence on STAT3 activation. PMID:15573129 JAK2-STAT3 pathway involeved in inhibition of DC activity. The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:24777831 STAT-3 phosphorylation was enhanced in IL-15 DCs compared to IL-4 DCs PMID:25582338 IL15 induces IFNG expression in DC via STAT3. PMID:20124100, PMID:9174615, PMID:11254683, PMID:9366401 Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10-mediated suppression. TNF and IFNG production in DC is STAT3 dependent. Probably downstream IL10. STAT3 downregulates MHC-II and CD86 surface expression downstream of IL10 and IL6, IL12, production. PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:14670306 Phosphorylation of the two isoforms of STAT3 (α and β) was detectable 15 min after stimulation with different doses of Flt3L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT3"/> <clone/> <bbox w="80.0" h="40.0" x="5825.0" y="1550.0"/> <glyph class="state variable" id="_526224ab-4626-4fc4-8628-0c1b249e7cfd"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="5817.5" y="1564.9681"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="s772_sa126" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 3 HUGO:STAT3 hgnc_id:HGNC:11364 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512, PMID:23894201 ‭The binding of IL-10 to its receptor activates JAK1 Two tyrosines‭ (‬Tyr‭ ‬446‭ ‬and Tyr‭ ‬496‭) ‬of IL-10RA are phosphorylated by the JAK1,‭ ‬to which the transcription factor STAT3‭ ‬binds via its SH2‭ ‬domain and in turn becomes itself phosphorylated. In DC Tyk2 has no influence on STAT3 activation. PMID:15573129 JAK2-STAT3 pathway involeved in inhibition of DC activity. The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:24777831 STAT-3 phosphorylation was enhanced in IL-15 DCs compared to IL-4 DCs PMID:25582338 IL15 induces IFNG expression in DC via STAT3. PMID:20124100, PMID:9174615, PMID:11254683, PMID:9366401 Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10-mediated suppression. TNF and IFNG production in DC is STAT3 dependent. Probably downstream IL10. STAT3 downregulates MHC-II and CD86 surface expression downstream of IL10 and IL6, IL12, production. PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:14670306 Phosphorylation of the two isoforms of STAT3 (α and β) was detectable 15 min after stimulation with different doses of Flt3L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT3"/> <bbox w="124.5" h="80.0" x="1432.75" y="1960.0"/> <glyph class="unit of information" id="_1c965185-20a7-467b-be6d-75bc2c6f02d5"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="1485.0" y="1955.0"/> </glyph> <glyph class="state variable" id="_95d4421b-ea40-4216-8d3a-95c04fee430e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1425.25" y="1994.9363"/> </glyph> </glyph> <glyph class="macromolecule" id="s96_sa151" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: NFKB inhibitor alpha HUGO:NFKBIA hgnc_id:HGNC:7797 HGNC:7797 ENTREZ:4792 UNIPROT:P25963 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10542212 The primary level of control of NFkB heterodimer is through its interaction with the inhibitorprotein NFKBIA (IkBa). IL10 inhibits TNF-dependent degradation of NFKBIA. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via prevention of degradation of IkBa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKBIA"/> <bbox w="80.0" h="40.0" x="4827.0" y="1389.5"/> <glyph class="state variable" id="_c94bdd2c-c367-4aea-b23d-55c45e14f431"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4819.5" y="1404.5"/> </glyph> </glyph> <glyph class="source and sink" id="s345_sa152" compartmentRef="c2_ca2"> <label text="s345"/> <bbox w="30.0" h="30.0" x="4996.5" y="1394.5"/> </glyph> <glyph class="macromolecule" id="s113_sa153" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: NFKB inhibitor alpha HUGO:NFKBIA hgnc_id:HGNC:7797 HGNC:7797 ENTREZ:4792 UNIPROT:P25963 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10542212 The primary level of control of NFkB heterodimer is through its interaction with the inhibitorprotein NFKBIA (IkBa). IL10 inhibits TNF-dependent degradation of NFKBIA. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via prevention of degradation of IkBa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKBIA"/> <bbox w="80.0" h="40.0" x="5086.0" y="1458.5"/> <glyph class="state variable" id="_92944716-83b6-42b6-a3f9-8258b69a004c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="5081.0" y="1473.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s19_sa154" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: HUGO:RELA HUGO:RELB Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876 NFkB signaling via RELA:p50 heterodimer provides expression of proinflamatory cytokines and realisation of M1 phenotype of macrophages. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via inhibition of p65 nuclear migration in inflammatory marophages PMID:10521409, PMID:18802069 The endogenous IKK complex, overexpressed IKKs, and recombinant IKKbeta efficiently phosphorylated the Ser536 residue of p65 in vivo and in vitro, that is important foe NFKB signaling activation. Ser536 is phoshorylated downstream of RAGE signaling in MDSC. PMID:9881974 RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="REL*"/> <bbox w="130.0" h="90.0" x="4410.0" y="1225.0"/> <glyph class="state variable" id="_e1a78b8f-d0c5-480b-9a33-807c33702db8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4405.0" y="1265.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s18_sa155" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: nuclear factor kappa B subunit 1 HUGO:NFKB1 hgnc_id:HGNC:7794 HGNC:7794 ENTREZ:4790 UNIPROT:P19838 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876, PMID:17145890 NFkB p50/p50 homodimers (which lack the transactivation domain) compete with canonical p65/p50 heterodimers for the binding sites on the inflammatory gene promoters, thereby blocking p65/p50 promoter binding and gene transcription. p50 NF-kappaB overexpression accounts for the inability of tumor assasiated macrophages to mount an effective M1 antitumor response capable of inhibiting tumor growth. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKB1_p50*"/> <bbox w="130.0" h="70.0" x="4125.0" y="1270.0"/> <glyph class="unit of information" id="_2126b68e-8183-4caf-b850-7cb976e5578f"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4165.0" y="1265.0"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="s546_sa156" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: nuclear factor kappa B subunit 1 HUGO:NFKB1 hgnc_id:HGNC:7794 HGNC:7794 ENTREZ:4790 UNIPROT:P19838 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876, PMID:17145890 NFkB p50/p50 homodimers (which lack the transactivation domain) compete with canonical p65/p50 heterodimers for the binding sites on the inflammatory gene promoters, thereby blocking p65/p50 promoter binding and gene transcription. p50 NF-kappaB overexpression accounts for the inability of tumor assasiated macrophages to mount an effective M1 antitumor response capable of inhibiting tumor growth. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKB1_p50*"/> <bbox w="120.75" h="80.75" x="4134.625" y="1399.625"/> <glyph class="unit of information" id="_cf67284c-442e-44d1-af58-42a0c6d37485"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="4185.0" y="1394.625"/> </glyph> <glyph class="unit of information" id="_aa6613d7-d950-45a0-a8d6-550aa1cbe218"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4170.0" y="1394.625"/> </glyph> </glyph> <glyph class="complex" id="s305_csa30" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:NFKB1_p50*:NFKBIA:REL* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RELA:p50/NFKBIA"/> <bbox w="115.0" h="175.0" x="5027.5" y="1172.5"/> <glyph class="macromolecule" id="s93_sa168"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: NFKB inhibitor alpha HUGO:NFKBIA hgnc_id:HGNC:7797 HGNC:7797 ENTREZ:4792 UNIPROT:P25963 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10542212 The primary level of control of NFkB heterodimer is through its interaction with the inhibitorprotein NFKBIA (IkBa). IL10 inhibits TNF-dependent degradation of NFKBIA. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via prevention of degradation of IkBa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKBIA"/> <bbox w="80.0" h="40.0" x="5045.0" y="1187.75"/> <glyph class="state variable" id="_90b1c6ac-4ffc-4fba-b685-1ce6cad0afa4"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="5040.0" y="1202.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s292_sa167"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: HUGO:RELA HUGO:RELB Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876 NFkB signaling via RELA:p50 heterodimer provides expression of proinflamatory cytokines and realisation of M1 phenotype of macrophages. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via inhibition of p65 nuclear migration in inflammatory marophages PMID:10521409, PMID:18802069 The endogenous IKK complex, overexpressed IKKs, and recombinant IKKbeta efficiently phosphorylated the Ser536 residue of p65 in vivo and in vitro, that is important foe NFKB signaling activation. Ser536 is phoshorylated downstream of RAGE signaling in MDSC. PMID:9881974 RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="REL*"/> <bbox w="80.0" h="40.0" x="5045.0" y="1237.75"/> <glyph class="state variable" id="_05336c5f-82a8-42c0-ac94-1f487f710bbc"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="5040.0" y="1252.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s307_sa166"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: nuclear factor kappa B subunit 1 HUGO:NFKB1 hgnc_id:HGNC:7794 HGNC:7794 ENTREZ:4790 UNIPROT:P19838 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876, PMID:17145890 NFkB p50/p50 homodimers (which lack the transactivation domain) compete with canonical p65/p50 heterodimers for the binding sites on the inflammatory gene promoters, thereby blocking p65/p50 promoter binding and gene transcription. p50 NF-kappaB overexpression accounts for the inability of tumor assasiated macrophages to mount an effective M1 antitumor response capable of inhibiting tumor growth. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKB1_p50*"/> <bbox w="80.0" h="40.0" x="5042.5" y="1279.5"/> <glyph class="unit of information" id="_515153ac-c104-4ea5-ae6c-6139f7e58c11"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="5057.5" y="1274.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s647_csa27" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CHUK:IKBKG:IKK_beta_* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: complex PMID‭:15145317 The activated IKK complex, catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of IkBa), polyubiquitination (at sites equivalent to Lys21 and Lys22 of IkBa) and subsequent degradation by the 26S proteasome. The released NF-kB dimers (in this pathway, most commonly the p50– RelA dimer) translocate to the nucleus, bind DNA and activate gene transcription PMID:10521409, PMID:18802069 The endogenous IKK complex, overexpressed IKKs, and recombinant IKKbeta efficiently phosphorylated the Ser536 residue of p65 in vivo and in vitro, that is important foe NFKB signaling activation.Ser536 is phoshorylated downstream of RAGE signaling in MDSC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IKK complex"/> <bbox w="100.0" h="164.0" x="4748.5" y="978.5"/> <glyph class="macromolecule" id="s648_sa159"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: conserved helix-loop-helix ubiquitous kinase HUGO:CHUK hgnc_id:HGNC:1974 HGNC:1974 ENTREZ:1147 UNIPROT:O15111 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17485448 TNIP3 (ABIN3‭) ‬inhibits IKK complex trough direct binding to IKBKG. It results in inhibition of‭ ‬FNKBIA phosphorylation and proteasomal degradation and prevents activation of downstream‭ ‬NFkB‭ ‬signaling‭ ‬downstream of IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CHUK"/> <bbox w="80.0" h="40.0" x="4758.5" y="1076.5"/> </glyph> <glyph class="macromolecule" id="s88_sa158"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: inhibitor of nuclear factor kappa B kinase subunit beta HUGO:IKBKB hgnc_id:HGNC:5960 HGNC:5960 ENTREZ:3551 UNIPROT:O14920 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17485448 TNIP3 (ABIN3‭) ‬inhibits IKK complex trough direct binding to IKBKG. It results in inhibition of‭ ‬FNKBIA phosphorylation and proteasomal degradation and prevents activation of downstream‭ ‬NFkB‭ ‬signaling‭ ‬downstream of IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IKKβ*"/> <bbox w="80.0" h="40.0" x="4757.5" y="1031.5"/> <glyph class="state variable" id="_28bbd8aa-5d20-434e-b83e-0a0497b011bb"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4752.5" y="1046.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s89_sa157"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: inhibitor of nuclear factor kappa B kinase subunit gamma HUGO:IKBKG hgnc_id:HGNC:5961 HGNC:5961 ENTREZ:8517 UNIPROT:Q9Y6K9 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17485448 TNIP3 (ABIN3‭) ‬inhibits IKK complex trough direct binding to IKBKG. It results in inhibition of‭ ‬FNKBIA phosphorylation and proteasomal degradation and prevents activation of downstream‭ ‬NFkB‭ ‬signaling‭ ‬downstream of IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IKBKG"/> <bbox w="80.0" h="40.0" x="4756.5" y="985.5"/> <glyph class="state variable" id="_1adf68cc-7ac1-4b0b-a416-53e2a7a01d67"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4831.5" y="1000.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s178_csa31" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:NFKB1_p50*:REL* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: 19171876 NFkB signaling via RELA:p50 heterodimer provides expression of proinflamatory cytokines and realisation of M1 phenotype of macrophages. 12193701, 11830590 CD40 expression is upregulated by STAT1 downstream of INFG and NF-kB downstream of TNF. 9841930 LPS induced nuclear translocation of the nuclear factor (NF)-kappaB transcription factor. Inhibition of NF-kappaB activation blocked maturation of DCs in terms of upregulation of major histocompatibility complex and costimulatory molecules. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RELA:p50"/> <bbox w="140.0" h="174.5" x="4525.0" y="1452.75"/> <glyph class="macromolecule" id="s235_sa170"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> HUGO:NFKB1 MODULE:DC PMID:19171876, PMID:17145890 NFkB p50/p50 homodimers (which lack the transactivation domain) compete with canonical p65/p50 heterodimers for the binding sites on the inflammatory gene promoters, thereby blocking p65/p50 promoter binding and gene transcription. p50 NF-kappaB overexpression accounts for the inability of tumor assasiated macrophages to mount an effective M1 antitumor response capable of inhibiting tumor growth. ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: nuclear factor kappa B subunit 1 HUGO:NFKB1 hgnc_id:HGNC:7794 HGNC:7794 ENTREZ:4790 UNIPROT:P19838 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876, PMID:17145890 NFkB p50/p50 homodimers (which lack the transactivation domain) compete with canonical p65/p50 heterodimers for the binding sites on the inflammatory gene promoters, thereby blocking p65/p50 promoter binding and gene transcription. p50 NF-kappaB overexpression accounts for the inability of tumor assasiated macrophages to mount an effective M1 antitumor response capable of inhibiting tumor growth. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKB1_p50*"/> <bbox w="118.5" h="66.5" x="4535.75" y="1534.0"/> <glyph class="unit of information" id="_9053639e-1b51-40f8-a0e4-59c895924750"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4570.0" y="1529.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s20_sa169"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: HUGO:RELA HUGO:RELB Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876 NFkB signaling via RELA:p50 heterodimer provides expression of proinflamatory cytokines and realisation of M1 phenotype of macrophages. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via inhibition of p65 nuclear migration in inflammatory marophages PMID:10521409, PMID:18802069 The endogenous IKK complex, overexpressed IKKs, and recombinant IKKbeta efficiently phosphorylated the Ser536 residue of p65 in vivo and in vitro, that is important foe NFKB signaling activation. Ser536 is phoshorylated downstream of RAGE signaling in MDSC. PMID:9881974 RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="REL*"/> <bbox w="120.5" h="58.5" x="4535.0" y="1468.75"/> <glyph class="state variable" id="_12735ed9-250b-4444-83db-5657f33de410"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4527.5" y="1493.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s236_sa175"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 10 HUGO:IL10 hgnc_id:HGNC:5962 HGNC:5962 ENTREZ:3586 UNIPROT:P22301 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming.PMID:18492954 mTOR regulates IL-12 expression through an autocrine action of IL-10 in DC via STAT3. PMID:15573129 DCs derived from transgenic mice that overexpress IL-10 markedly suppressed allogeneic T-cell responses, CTL responses and IL-12 production70. IL-10 might convert iDCs into tolerogenic APCs through decreased expression of co-stimulatory molecules PMID:11254683, PMID:9366401 Mature DCs become resistant to the effects of exogenous IL-10, addition of anti-IL-10 mAb to already matured DCs had no influence on cytokine release and surface phenotype. Mature DCs show enhanced accumulation of IL-10R1 mRNA and intracellular IL-10R protein but reduced membrane IL-10R and IL-10 binding activity. IL10 signaling activates STAT3 in DC PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) PMID:25446896 Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10"/> <bbox w="80.0" h="40.0" x="176.0" y="1175.0"/> </glyph> <glyph class="complex" id="s185_csa33" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL10:IL10RA:IL10RB Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10R/IL10"/> <bbox w="180.0" h="131.0" x="445.0" y="1484.5"/> <glyph class="macromolecule" id="s50_sa177"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 HUGO:IL10 hgnc_id:HGNC:5962 HGNC:5962 ENTREZ:3586 UNIPROT:P22301 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming.PMID:18492954 mTOR regulates IL-12 expression through an autocrine action of IL-10 in DC via STAT3. PMID:15573129 DCs derived from transgenic mice that overexpress IL-10 markedly suppressed allogeneic T-cell responses, CTL responses and IL-12 production70. IL-10 might convert iDCs into tolerogenic APCs through decreased expression of co-stimulatory molecules PMID:11254683, PMID:9366401 Mature DCs become resistant to the effects of exogenous IL-10, addition of anti-IL-10 mAb to already matured DCs had no influence on cytokine release and surface phenotype. Mature DCs show enhanced accumulation of IL-10R1 mRNA and intracellular IL-10R protein but reduced membrane IL-10R and IL-10 binding activity. IL10 signaling activates STAT3 in DC PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) PMID:25446896 Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10"/> <bbox w="80.0" h="40.0" x="455.0" y="1496.0"/> </glyph> <glyph class="macromolecule" id="s49_sa178"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 receptor subunit beta HUGO:IL10RB hgnc_id:HGNC:5965 HGNC:5965 ENTREZ:3588 UNIPROT:Q08334 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10RB"/> <bbox w="80.0" h="50.0" x="536.0" y="1536.5"/> <glyph class="unit of information" id="_28142055-91ff-4c93-88e2-0ecb7567873f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="553.5" y="1531.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s48_sa179"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 receptor subunit alpha HUGO:IL10RA hgnc_id:HGNC:5964 HGNC:5964 ENTREZ:3587 UNIPROT:Q13651 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10RA"/> <bbox w="80.0" h="50.0" x="460.0" y="1536.5"/> <glyph class="state variable" id="_0fd52d54-cc43-47ec-b196-1679732e9c24"> <state value="" variable="Y496"/> <bbox w="30.0" h="10.0" x="445.0" y="1538.3364"/> </glyph> <glyph class="state variable" id="_e1e24f4d-5eca-4240-a1d5-b0fd9606fc6d"> <state value="" variable="Y446"/> <bbox w="30.0" h="10.0" x="487.15808" y="1581.5"/> </glyph> <glyph class="unit of information" id="_fceaed5f-9bbe-40cc-8f09-ffa4eddab4eb"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="477.5" y="1531.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s184_csa34" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL10RA:IL10RB Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10R contains two subunits IL1ORA and IL10RB PMID:‭15833879 ‭Anti IL-10 receptor–specific antibody switched TAMs from an M2 to an M1 macrophage–like phenotype. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10R"/> <bbox w="179.0" h="107.0" x="355.5" y="1726.5"/> <glyph class="macromolecule" id="s42_sa180"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 receptor subunit beta HUGO:IL10RB hgnc_id:HGNC:5965 HGNC:5965 ENTREZ:3588 UNIPROT:Q08334 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10RB"/> <bbox w="80.0" h="50.0" x="448.5" y="1757.5"/> <glyph class="unit of information" id="_fb2e705d-73ff-467a-971c-0c0e0426d180"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="466.0" y="1752.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s41_sa181"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 receptor subunit alpha HUGO:IL10RA hgnc_id:HGNC:5964 HGNC:5964 ENTREZ:3587 UNIPROT:Q13651 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10RA"/> <bbox w="80.0" h="50.0" x="364.5" y="1759.5"/> <glyph class="state variable" id="_21eae6dc-f8e5-40d6-b0eb-735de3113509"> <state value="" variable="Y496"/> <bbox w="30.0" h="10.0" x="349.5" y="1761.3364"/> </glyph> <glyph class="state variable" id="_69048281-327a-461c-917f-0b1c5aa202ea"> <state value="" variable="Y446"/> <bbox w="30.0" h="10.0" x="391.65808" y="1804.5"/> </glyph> <glyph class="unit of information" id="_925fdc24-3ec9-40d3-b5f6-67ff4baacd73"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="382.0" y="1754.5"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s301_csa35" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL10:IL10RA:IL10RB:JAK1 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:‭21115385, PMID:7543512 ‭The binding of IL-10 to its receptor activates JAK1 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10R/IL10/JAK1"/> <bbox w="179.0" h="177.0" x="755.5" y="1481.5"/> <glyph class="macromolecule" id="s304_sa182"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 HUGO:IL10 hgnc_id:HGNC:5962 HGNC:5962 ENTREZ:3586 UNIPROT:P22301 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming.PMID:18492954 mTOR regulates IL-12 expression through an autocrine action of IL-10 in DC via STAT3. PMID:15573129 DCs derived from transgenic mice that overexpress IL-10 markedly suppressed allogeneic T-cell responses, CTL responses and IL-12 production70. IL-10 might convert iDCs into tolerogenic APCs through decreased expression of co-stimulatory molecules PMID:11254683, PMID:9366401 Mature DCs become resistant to the effects of exogenous IL-10, addition of anti-IL-10 mAb to already matured DCs had no influence on cytokine release and surface phenotype. Mature DCs show enhanced accumulation of IL-10R1 mRNA and intracellular IL-10R protein but reduced membrane IL-10R and IL-10 binding activity. IL10 signaling activates STAT3 in DC PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) PMID:25446896 Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10"/> <bbox w="80.0" h="40.0" x="768.5" y="1486.0"/> </glyph> <glyph class="macromolecule" id="s303_sa183"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 receptor subunit beta HUGO:IL10RB hgnc_id:HGNC:5965 HGNC:5965 ENTREZ:3588 UNIPROT:Q08334 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10RB"/> <bbox w="80.0" h="50.0" x="845.5" y="1533.5"/> <glyph class="unit of information" id="_a65971a3-53eb-4f44-bab2-1c24842e0074"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="863.0" y="1528.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s302_sa185"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="771.5" y="1592.0"/> <glyph class="state variable" id="_60c7a726-16a4-4b8a-b489-6e225c889f60"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="764.0" y="1607.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s64_sa189"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 10 receptor subunit alpha HUGO:IL10RA hgnc_id:HGNC:5964 HGNC:5964 ENTREZ:3587 UNIPROT:Q13651 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10RA"/> <bbox w="80.0" h="50.0" x="765.0" y="1535.0"/> <glyph class="state variable" id="_c125d75d-4615-4f38-950e-0841638dfdad"> <state value="P" variable="Y496"/> <bbox w="35.0" h="10.0" x="747.5" y="1536.8364"/> </glyph> <glyph class="state variable" id="_4ea6a06c-a53a-4fc5-94c4-40baed90e949"> <state value="P" variable="Y446"/> <bbox w="35.0" h="10.0" x="789.6581" y="1580.0"/> </glyph> <glyph class="unit of information" id="_17add05a-6520-411b-af4e-fb68d4e4ec79"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="782.5" y="1530.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s547_sa205"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: transforming growth factor beta 1 HUGO:TGFB1 hgnc_id:HGNC:11766 HGNC:11766 ENTREZ:7040 UNIPROT:P01137 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:22703233 TGFB1 participates in M2 activation. PMID:7594497 TGFB1 upregulates IL10 expression in macrophages. TGFB1 and IL10 dowregulate expression of TNF. PMID:21278795 TGFB-induced IRAK3 (IRAK-M) expression in tumor-associated macrophages and inhibit TLR-dependent signaling PMID:20644162 Cytokine-induced CD33+ human MDSCs have upregulated iNOS, TGFβ, VEGF. PMID:19109155 MDSC inhibit cytotoxicity, NKG2D expression, and IFN-gamma production of NK cells both in vitro and in vivo. Membrane-bound TGF-beta1 on MDSC is responsible for MDSC-mediated suppression of NK cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TGFB1"/> <bbox w="80.0" h="40.0" x="1155.0" y="580.0"/> </glyph> <glyph class="macromolecule" id="s548_sa206" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: transforming growth factor beta receptor 2 HUGO:TGFBR2 hgnc_id:HGNC:11773 HGNC:11773 ENTREZ:7048 UNIPROT:P37173 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:22703233 TGFBR2 upregulates expression of markers M2 activation as ARG1, MCR2 and LGALS3 (galecsin3) and induces AKT activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TGFBR2"/> <bbox w="80.0" h="50.0" x="1415.0" y="805.0"/> <glyph class="unit of information" id="_08dc2604-a49e-4bc0-9895-c9479648a72c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1432.5" y="800.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s851_sa207" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: transforming growth factor beta receptor 1 HUGO:TGFBR1 hgnc_id:HGNC:11772 HGNC:11772 ENTREZ:7046 UNIPROT:P36897 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:12809600 A TGFB ligand initiates signaling by binding to and bringing together type I and type II receptor serine/threonine kinases on the cell surface. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TGFBR1"/> <bbox w="80.0" h="50.0" x="1295.0" y="825.0"/> <glyph class="unit of information" id="_9544aea5-a2a4-46d7-914c-0968bd2fdd69"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1312.5" y="820.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1359_sa208" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: SMAD family member 2 HUGO:SMAD2 hgnc_id:HGNC:6768 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. PMID:21042762 Inhibition of TGF-ß signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD2"/> <bbox w="80.0" h="40.0" x="1655.0" y="1180.0"/> <glyph class="state variable" id="_0f8a68cd-144c-4a63-b4a3-5a054a3ae0b2"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1650.0" y="1194.9681"/> </glyph> </glyph> <glyph class="macromolecule" id="s1358_sa209" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: SMAD family member 2 HUGO:SMAD2 hgnc_id:HGNC:6768 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. PMID:21042762 Inhibition of TGF-ß signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD2"/> <bbox w="80.0" h="40.0" x="1655.0" y="1260.0"/> <glyph class="state variable" id="_97c64e5d-ebf7-4172-adb7-b0023e321a18"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1647.5" y="1274.9681"/> </glyph> </glyph> <glyph class="macromolecule" id="s1331_sa210" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: SMAD family member 4 HUGO:SMAD4 hgnc_id:HGNC:6770 HGNC:6770 ENTREZ:4089 UNIPROT:Q13485 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD4"/> <bbox w="80.0" h="40.0" x="1775.0" y="1240.0"/> </glyph> <glyph class="macromolecule" id="s1312_sa212" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: SMAD family member 3 HUGO:SMAD3 hgnc_id:HGNC:6769 HGNC:6769 ENTREZ:4088 UNIPROT:P84022 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. PMID:21042762 Inhibition of TGF-ß signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs. Smad2/3 somehow suppresses IRF3 phosphorylation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD3"/> <bbox w="80.0" h="40.0" x="1883.0" y="1120.0"/> <glyph class="state variable" id="_899b9317-407f-4ccc-9b80-dc853da33aa1"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1878.0" y="1135.0"/> </glyph> </glyph> <glyph class="complex" id="s852_csa40" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TGFB1:TGFBR1:TGFBR2 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:12809600 A TGFB ligand initiates signaling by binding to and bringing together type I and type II receptor serine/threonine kinases on the cell surface. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s852"/> <bbox w="200.0" h="120.0" x="1435.0" y="980.0"/> <glyph class="macromolecule" id="s855_sa213"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: transforming growth factor beta 1 HUGO:TGFB1 hgnc_id:HGNC:11766 HGNC:11766 ENTREZ:7040 UNIPROT:P01137 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:22703233 TGFB1 participates in M2 activation. PMID:7594497 TGFB1 upregulates IL10 expression in macrophages. TGFB1 and IL10 dowregulate expression of TNF. PMID:21278795 TGFB-induced IRAK3 (IRAK-M) expression in tumor-associated macrophages and inhibit TLR-dependent signaling PMID:20644162 Cytokine-induced CD33+ human MDSCs have upregulated iNOS, TGFβ, VEGF. PMID:19109155 MDSC inhibit cytotoxicity, NKG2D expression, and IFN-gamma production of NK cells both in vitro and in vivo. Membrane-bound TGF-beta1 on MDSC is responsible for MDSC-mediated suppression of NK cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TGFB1"/> <bbox w="80.0" h="40.0" x="1545.0" y="1000.0"/> </glyph> <glyph class="macromolecule" id="s854_sa214"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: transforming growth factor beta receptor 1 HUGO:TGFBR1 hgnc_id:HGNC:11772 HGNC:11772 ENTREZ:7046 UNIPROT:P36897 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:12809600 A TGFB ligand initiates signaling by binding to and bringing together type I and type II receptor serine/threonine kinases on the cell surface. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TGFBR1"/> <bbox w="80.0" h="50.0" x="1545.0" y="1045.0"/> <glyph class="unit of information" id="_3f128e6c-2c6e-489a-b328-ddd059494507"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1562.5" y="1040.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s853_sa215"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: transforming growth factor beta receptor 2 HUGO:TGFBR2 hgnc_id:HGNC:11773 HGNC:11773 ENTREZ:7048 UNIPROT:P37173 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:22703233 TGFBR2 upregulates expression of markers M2 activation as ARG1, MCR2 and LGALS3 (galecsin3) and induces AKT activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TGFBR2"/> <bbox w="80.0" h="50.0" x="1455.0" y="1045.0"/> <glyph class="unit of information" id="_038a31d2-7ccb-4729-bd74-d53a7ee8c4cc"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1472.5" y="1040.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s1332_csa41" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:SMAD3:SMAD4 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: 11792802, 12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocatio References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1332"/> <bbox w="100.0" h="120.0" x="1875.0" y="1310.0"/> <glyph class="macromolecule" id="s1334_sa216"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: SMAD family member 3 HUGO:SMAD3 hgnc_id:HGNC:6769 HGNC:6769 ENTREZ:4088 UNIPROT:P84022 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. PMID:21042762 Inhibition of TGF-ß signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs. Smad2/3 somehow suppresses IRF3 phosphorylation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD3"/> <bbox w="80.0" h="40.0" x="1885.0" y="1320.0"/> <glyph class="state variable" id="_d933ed52-137c-4ad2-a487-14915a01a3a2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1877.5" y="1335.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1333_sa217"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: SMAD family member 4 HUGO:SMAD4 hgnc_id:HGNC:6770 HGNC:6770 ENTREZ:4089 UNIPROT:Q13485 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD4"/> <bbox w="80.0" h="40.0" x="1885.0" y="1360.0"/> </glyph> </glyph> <glyph class="complex" id="s1360_csa42" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:SMAD2:SMAD4 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1360"/> <bbox w="100.0" h="120.0" x="1695.0" y="1360.0"/> <glyph class="macromolecule" id="s1361_sa218"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: SMAD family member 4 HUGO:SMAD4 hgnc_id:HGNC:6770 HGNC:6770 ENTREZ:4089 UNIPROT:Q13485 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD4"/> <bbox w="80.0" h="40.0" x="1705.0" y="1410.0"/> </glyph> <glyph class="macromolecule" id="s1362_sa219"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: SMAD family member 2 HUGO:SMAD2 hgnc_id:HGNC:6768 HGNC:6768 ENTREZ:4087 UNIPROT:Q15796 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. PMID:21042762 Inhibition of TGF-ß signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD2"/> <bbox w="80.0" h="40.0" x="1705.0" y="1370.0"/> <glyph class="state variable" id="_39305e84-4a7c-4ebf-b961-6a887cb87f66"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1697.5" y="1384.9681"/> </glyph> </glyph> </glyph> <glyph class="phenotype" id="s3_sa220"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:15573129 There are increased numbers of immature DCs in the peripheral blood of patients with cancer and in tumour tissues References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Imature_DC_phenotype"/> <bbox w="345.0" h="132.5" x="1142.5" y="3743.75"/> </glyph> <glyph class="phenotype" id="s4_sa221" compartmentRef="c10_ca10"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:15573129 Necrotic tumour cells activate DCs (that is, promote maturation), which results in the upregulation of expression of MHC class II molecules and co-stimulatory molecules (such as CD80 and CD86) at the cell-surface of DCs. These cells also express MHC class I molecules. Activated DCs migrate to the draining lymph nodes, where they interact with CD4+ and CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Mature_DC_phenotype"/> <bbox w="400.0" h="135.0" x="5525.0" y="2652.5"/> </glyph> <glyph class="phenotype" id="s5_sa222"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="T-cell_activation"/> <bbox w="380.0" h="125.0" x="5625.0" y="3977.5"/> </glyph> <glyph class="macromolecule" id="s534_sa226" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD86 molecule HUGO:CD86 hgnc_id:HGNC:1705 HGNC:1705 ENTREZ:942 UNIPROT:P42081 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:20805416 Expression of CD86, a critical costimulatory molecule for efficient T cell priming, is enhanced in activated mDCs during mTOR inhibition This phenotype was not observed in moDCs, in which surface expression of CD80 and CD86 was inhibited by rapamycin. PMID:11964292,PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:22437870 CD80 and CD86 act lic coactivators of T-cells when they interact with CD28 and inhibit T-cells via interactions with CTLA4 PMID:10477595, PMID:8920882, PMID: 25215878 FLT3L induces Ag-presenting ability of Dcs. Probably via induction of surface expression of class II MHC and CD86. PMID:22076556, PMID:21220452, PMID:24218453 In immature DCs, internalization of MHC class II molecules from the plasma membrane may require the ubiquitin ligase MARCH1, which is controlled by interleukin-10 (IL-10). CD83 on mature DCs prevents this ubiquitylation of MHC class II molecules and thus stabilizes MHC class II molecules on the cell surface. Addidionally it prevents CD86 ubiquitinqtion. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD86"/> <bbox w="80.0" h="40.0" x="4635.0" y="3340.0"/> <glyph class="state variable" id="_eedab750-75e7-4902-87b4-a23b032a2175"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4630.0" y="3355.0"/> </glyph> <glyph class="unit of information" id="_5fc69489-3e39-4c8a-9a65-b8a8f7b61f69"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4652.5" y="3335.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s9_sa230"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 2 HUGO:IL2 hgnc_id:HGNC:6001 HGNC:6001 ENTREZ:3558 UNIPROT:P60568 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24829413, PMID:15289500 IL-2 increases the ability of DCs to activate allogeneic CD8+ T Also dendritic cell-derived IL-2 for NK cell activation. PMID:24829413 IL-2 phosphorylates STAT5 to drive IFN-γ production and activation of human dendritic cells. PMID:15353479 Human and mouse DCs produce IL-2 downstream of IL15+CD40L signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2"/> <bbox w="80.0" h="40.0" x="7355.0" y="1680.0"/> </glyph> <glyph class="macromolecule" id="s12_sa231"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MOK protein kinase HUGO:MOK hgnc_id:HGNC:9833 HGNC:9833 ENTREZ:5891 UNIPROT:Q9UQ07 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:9510252 Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs PMID:17948027, PMID:22437871, PMID:17204652 Dendritic Cells are critical Antigen-Presenting Cells in tumor Immunity. They present processed protein and lipid antigens to T cells via both classical (major histocompatibility complex (MHC) class I and class II) and non-classical (CD1 family) antigen-presenting molecules. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57). Additionally, after antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. PMID:10837075 Immature DCs are very efficient in Ag capture and can use several pathways, such as (a) macropinocytosis; (b) receptor-mediated endocytosis via C-type lectin receptors (mannose receptor, DEC-205) or Fcγ receptor types I (CD64) and II (CD32) [uptake of immune complexes or opsonized particles ]; and (c) phagocytosis of particles such as latex beads , apoptotic and necrotic cell fragments (involving CD36 and αvβ3 or αvβ5 integrins), viruses, and bacteria including mycobacteria, as well as intracellular parasites such as Leishmania major. DCs can also internalize the peptide loaded heat shock proteins gp96 and Hsp70 through presently unknown mechanisms References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen"/> <bbox w="80.0" h="40.0" x="4170.0" y="4215.0"/> </glyph> <glyph class="macromolecule" id="s13_sa232" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MOK protein kinase HUGO:MOK hgnc_id:HGNC:9833 HGNC:9833 ENTREZ:5891 UNIPROT:Q9UQ07 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:9510252 Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs PMID:17948027, PMID:22437871, PMID:17204652 Dendritic Cells are critical Antigen-Presenting Cells in tumor Immunity. They present processed protein and lipid antigens to T cells via both classical (major histocompatibility complex (MHC) class I and class II) and non-classical (CD1 family) antigen-presenting molecules. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57). Additionally, after antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. PMID:10837075 Immature DCs are very efficient in Ag capture and can use several pathways, such as (a) macropinocytosis; (b) receptor-mediated endocytosis via C-type lectin receptors (mannose receptor, DEC-205) or Fcγ receptor types I (CD64) and II (CD32) [uptake of immune complexes or opsonized particles ]; and (c) phagocytosis of particles such as latex beads , apoptotic and necrotic cell fragments (involving CD36 and αvβ3 or αvβ5 integrins), viruses, and bacteria including mycobacteria, as well as intracellular parasites such as Leishmania major. DCs can also internalize the peptide loaded heat shock proteins gp96 and Hsp70 through presently unknown mechanisms References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen"/> <bbox w="80.0" h="40.0" x="2735.0" y="2200.0"/> </glyph> <glyph class="macromolecule" id="s14_sa234" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="2715.0" y="1860.0"/> <glyph class="unit of information" id="_4a7d5902-f2f9-4ef9-9e69-945b10d33a41"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="2730.0" y="1855.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s22_sa238" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: legumain HUGO:LGMN hgnc_id:HGNC:9472 HGNC:9472 ENTREZ:5641 UNIPROT:Q99538 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181339, PMID:12705852 Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L PMID:12776207, PMID:10795737, PMID:17204652 Cathepsins B,D,L, S and AEP (LGMN) are the lysosomal proteases implicated in antigen presentation in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LGMN"/> <bbox w="80.0" h="40.0" x="2815.0" y="2150.0"/> </glyph> <glyph class="macromolecule" id="s23_sa239" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cathepsin L HUGO:CTSL hgnc_id:HGNC:2537 HGNC:2537 ENTREZ:1514 UNIPROT:P07711 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:22157818 CTSS (cathepsin S), CTSB (cathepsin B) and CTSL (cathepsin L) are active in DC phagosomes. Phagosomal NOX2 activity via ROS inhibits the activities of local cysteine (B/S/L ), but not aspartic (D/E), cathepsins PMID:12776207 Cathepsins B,D,L, S and AEP (LGMN) are the lysosomal proteases implicated in antigen presentation in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CTSL"/> <bbox w="80.0" h="40.0" x="2625.0" y="1950.0"/> </glyph> <glyph class="macromolecule" id="s24_sa240" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cathepsin S HUGO:CTSS hgnc_id:HGNC:2545 HGNC:2545 ENTREZ:1520 UNIPROT:P25774 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22157818 CTSS (cathepsin S), CTSB (cathepsin B) and CTSL (cathepsin L) are active in DC phagosomes. Phagosomal NOX2 activity via ROS inhibits the activities of local cysteine (B/S/L ), but not aspartic (D/E), cathepsins PMID:22424724 Cathepsin S dominates autoantigen processing in human thymic dendritic cells. PMID:10072073, PMID:10562280 Cathepsin S provides Ii (CD74) degradation in dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CTSS"/> <bbox w="80.0" h="40.0" x="2825.0" y="2090.0"/> </glyph> <glyph class="macromolecule" id="s25_sa241" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: IFI30, lysosomal thiol reductase HUGO:IFI30 hgnc_id:HGNC:5398 HGNC:5398 ENTREZ:10437 UNIPROT:P13284 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:11701933, PMID:12198183, PMID:10639150, PMID:17142755, PMID:17204652 Gamma-interferon-inducible lysosomal thiol reductase IFI30 (GILT) facilitates unfolding of endocytosed antigens in MHC class II -containing compartments by enzymatic cleavage of disulfide bonds in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFI30"/> <bbox w="80.0" h="40.0" x="2604.0" y="2120.0"/> </glyph> <glyph class="macromolecule" id="s30_sa245" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MOK protein kinase HUGO:MOK hgnc_id:HGNC:9833 HGNC:9833 ENTREZ:5891 UNIPROT:Q9UQ07 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:9510252 Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs PMID:17948027, PMID:22437871, PMID:17204652 Dendritic Cells are critical Antigen-Presenting Cells in tumor Immunity. They present processed protein and lipid antigens to T cells via both classical (major histocompatibility complex (MHC) class I and class II) and non-classical (CD1 family) antigen-presenting molecules. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57). Additionally, after antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. PMID:10837075 Immature DCs are very efficient in Ag capture and can use several pathways, such as (a) macropinocytosis; (b) receptor-mediated endocytosis via C-type lectin receptors (mannose receptor, DEC-205) or Fcγ receptor types I (CD64) and II (CD32) [uptake of immune complexes or opsonized particles ]; and (c) phagocytosis of particles such as latex beads , apoptotic and necrotic cell fragments (involving CD36 and αvβ3 or αvβ5 integrins), viruses, and bacteria including mycobacteria, as well as intracellular parasites such as Leishmania major. DCs can also internalize the peptide loaded heat shock proteins gp96 and Hsp70 through presently unknown mechanisms References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen"/> <bbox w="80.0" h="40.0" x="3665.0" y="2370.0"/> </glyph> <glyph class="macromolecule" id="s31_sa246" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="3405.0" y="2370.0"/> <glyph class="unit of information" id="_4885b211-5409-43a9-8019-d99c44bbe4e8"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="3420.0" y="2365.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s33_sa248" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="4235.0" y="2730.0"/> <glyph class="unit of information" id="_cbfa5119-956f-4161-8374-3164d88ecf94"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4250.0" y="2725.0"/> </glyph> </glyph> <glyph class="complex" id="s35_csa45" compartmentRef="c10_ca10"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:B2M:MHC class I*:Tumor_antigen_fragment Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s35"/> <bbox w="200.0" h="125.0" x="4285.0" y="2987.5"/> <glyph class="macromolecule" id="s1830_sa250"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="50.0" x="4305.0" y="3042.5"/> <glyph class="state variable" id="_f241d47c-1862-483f-ae65-738466e06d2d"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4300.0" y="3062.5"/> </glyph> <glyph class="unit of information" id="_ecf91dea-c0f6-46c2-8f24-b32f47e51cb7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4322.5" y="3037.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1831_sa251"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="4305.0" y="2997.5"/> <glyph class="unit of information" id="_59c9086b-b23f-4cb2-9be5-717d3ca4751d"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4320.0" y="2992.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1832_sa258"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="4395.0" y="3042.5"/> </glyph> </glyph> <glyph class="complex" id="s45_csa28" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:NFKB1_p50*:NFKBIA:REL* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RELA:p50/NFKBIA"/> <bbox w="115.0" h="175.0" x="4731.0" y="1183.0"/> <glyph class="macromolecule" id="s101_sa162"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: NFKB inhibitor alpha HUGO:NFKBIA hgnc_id:HGNC:7797 HGNC:7797 ENTREZ:4792 UNIPROT:P25963 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10542212 The primary level of control of NFkB heterodimer is through its interaction with the inhibitorprotein NFKBIA (IkBa). IL10 inhibits TNF-dependent degradation of NFKBIA. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via prevention of degradation of IkBa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKBIA"/> <bbox w="80.0" h="40.0" x="4744.5" y="1199.0"/> <glyph class="state variable" id="_255b5865-fdeb-4ca9-a96e-3b6ce60a1e3d"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4737.0" y="1214.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s306_sa161"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: HUGO:RELA HUGO:RELB Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876 NFkB signaling via RELA:p50 heterodimer provides expression of proinflamatory cytokines and realisation of M1 phenotype of macrophages. PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via inhibition of p65 nuclear migration in inflammatory marophages PMID:10521409, PMID:18802069 The endogenous IKK complex, overexpressed IKKs, and recombinant IKKbeta efficiently phosphorylated the Ser536 residue of p65 in vivo and in vitro, that is important foe NFKB signaling activation. Ser536 is phoshorylated downstream of RAGE signaling in MDSC. PMID:9881974 RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="REL*"/> <bbox w="80.0" h="40.0" x="4743.5" y="1242.0"/> <glyph class="state variable" id="_b517c413-f57d-4c15-b8fd-294e08a02c89"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4736.0" y="1257.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s46_sa160"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: nuclear factor kappa B subunit 1 HUGO:NFKB1 hgnc_id:HGNC:7794 HGNC:7794 ENTREZ:4790 UNIPROT:P19838 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:19171876, PMID:17145890 NFkB p50/p50 homodimers (which lack the transactivation domain) compete with canonical p65/p50 heterodimers for the binding sites on the inflammatory gene promoters, thereby blocking p65/p50 promoter binding and gene transcription. p50 NF-kappaB overexpression accounts for the inability of tumor assasiated macrophages to mount an effective M1 antitumor response capable of inhibiting tumor growth. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NFKB1_p50*"/> <bbox w="80.0" h="40.0" x="4746.0" y="1290.0"/> <glyph class="unit of information" id="_22a2cb35-1d38-405a-b734-60c2a3443a44"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4761.0" y="1285.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s47_csa29" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CHUK:IKBKG:IKK_beta_* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: complex PMID‭:15145317 The activated IKK complex, catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of IkBa), polyubiquitination (at sites equivalent to Lys21 and Lys22 of IkBa) and subsequent degradation by the 26S proteasome. The released NF-kB dimers (in this pathway, most commonly the p50– RelA dimer) translocate to the nucleus, bind DNA and activate gene transcription PMID:15573129 NF-B is required for the development of DCs Blocking NF-B activity been shown to prevent DC differentiation from progenitor cells in vitro. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IKK complex"/> <bbox w="100.0" h="164.0" x="4945.0" y="978.0"/> <glyph class="macromolecule" id="s51_sa165"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: conserved helix-loop-helix ubiquitous kinase HUGO:CHUK hgnc_id:HGNC:1974 HGNC:1974 ENTREZ:1147 UNIPROT:O15111 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17485448 TNIP3 (ABIN3‭) ‬inhibits IKK complex trough direct binding to IKBKG. It results in inhibition of‭ ‬FNKBIA phosphorylation and proteasomal degradation and prevents activation of downstream‭ ‬NFkB‭ ‬signaling‭ ‬downstream of IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CHUK"/> <bbox w="80.0" h="40.0" x="4951.5" y="1077.25"/> </glyph> <glyph class="macromolecule" id="s650_sa164"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: inhibitor of nuclear factor kappa B kinase subunit beta HUGO:IKBKB hgnc_id:HGNC:5960 HGNC:5960 ENTREZ:3551 UNIPROT:O14920 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17485448 TNIP3 (ABIN3‭) ‬inhibits IKK complex trough direct binding to IKBKG. It results in inhibition of‭ ‬FNKBIA phosphorylation and proteasomal degradation and prevents activation of downstream‭ ‬NFkB‭ ‬signaling‭ ‬downstream of IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IKKβ*"/> <bbox w="80.0" h="40.0" x="4951.5" y="1037.25"/> <glyph class="state variable" id="_23842b42-f367-4750-b8b6-4d60e58d2b06"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4944.0" y="1052.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s649_sa163"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: inhibitor of nuclear factor kappa B kinase subunit gamma HUGO:IKBKG hgnc_id:HGNC:5961 HGNC:5961 ENTREZ:8517 UNIPROT:Q9Y6K9 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17485448 TNIP3 (ABIN3‭) ‬inhibits IKK complex trough direct binding to IKBKG. It results in inhibition of‭ ‬FNKBIA phosphorylation and proteasomal degradation and prevents activation of downstream‭ ‬NFkB‭ ‬signaling‭ ‬downstream of IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IKBKG"/> <bbox w="80.0" h="40.0" x="4953.0" y="985.0"/> <glyph class="state variable" id="_c2930408-eccd-44d7-869a-23d55b881c8d"> <state value="Ub" variable=""/> <bbox w="20.0" h="10.0" x="5023.0" y="1000.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s52_csa47" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:B2M:MHC class I*:Tumor_antigen_fragment Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s35"/> <bbox w="230.0" h="135.0" x="4110.0" y="3632.5"/> <glyph class="macromolecule" id="s37_sa256"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="4130.0" y="3642.5"/> <glyph class="unit of information" id="_62092df1-6d42-442e-8cd5-211f0ffdf29d"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4145.0" y="3637.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s36_sa257"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="50.0" x="4130.0" y="3687.5"/> <glyph class="state variable" id="_cd27e84f-4a15-44b3-92f0-38dea04bc880"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4125.0" y="3707.5"/> </glyph> <glyph class="unit of information" id="_fc9c0889-ce81-4764-8ff7-56c1d80ea256"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4147.5" y="3682.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1835_sa299"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="4220.0" y="3687.5"/> </glyph> </glyph> <glyph class="complex" id="s55_csa48" compartmentRef="c10_ca10"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TAP1:TAP2:TAPASIN* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s55"/> <bbox w="172.5" h="110.0" x="3918.75" y="2495.0"/> <glyph class="macromolecule" id="s1823_sa243"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: transporter 1, ATP binding cassette subfamily B member HUGO:TAP1 hgnc_id:HGNC:43 HGNC:43 ENTREZ:6890 UNIPROT:Q03518 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Antigen peptides are transported into the ER from the cytosol via TAPs PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting. TAP-mediates peptide transport and loading on MHC class I in purified phagosomes. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAP1"/> <bbox w="80.0" h="40.0" x="3921.25" y="2505.0"/> </glyph> <glyph class="macromolecule" id="s1824_sa244"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: transporter 2, ATP binding cassette subfamily B member HUGO:TAP2 hgnc_id:HGNC:44 HGNC:44 ENTREZ:6891 UNIPROT:Q03519 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Antigen peptides are transported into the ER from the cytosol via TAPs, tapasin stabilizes the TAP1/TAP2 heterodimer. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. TAP-mediates peptide transport and loading on MHC class I in purified phagosomes. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAP2"/> <bbox w="80.0" h="40.0" x="3923.75" y="2545.0"/> </glyph> <glyph class="macromolecule" id="s1825_sa249"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TAP binding protein HUGO:TAPBP hgnc_id:HGNC:11566 HGNC:11566 ENTREZ:6892 UNIPROT:O15533 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333 Tapasin stabilizes the TAP1/TAP2 heterodimer PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation. PMID:10973281 Tapasin may have a quantitative effect on the peptide loading process as suggested by the impaired antigen presentation by DCs from Tpn-/- mice. dendritic cells of tapasin-deficient mice do not cross-present protein antigen via the MHC class I pathway. PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAPASIN*"/> <bbox w="80.0" h="40.0" x="4005.0" y="2540.0"/> </glyph> </glyph> <glyph class="complex" id="s59_csa49" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CANX:MHC class I* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s59"/> <bbox w="100.0" h="120.0" x="4850.0" y="2588.75"/> <glyph class="macromolecule" id="s57_sa259"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: calnexin HUGO:CANX hgnc_id:HGNC:1473 HGNC:1473 ENTREZ:821 UNIPROT:P27824 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CANX"/> <bbox w="80.0" h="40.0" x="4860.0" y="2598.75"/> </glyph> <glyph class="macromolecule" id="s58_sa260"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="50.0" x="4860.0" y="2643.75"/> <glyph class="state variable" id="_d6104e20-5dd4-4e2a-8f0a-eaa9839bca08"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4855.0" y="2663.75"/> </glyph> <glyph class="unit of information" id="_18ed04a5-2e81-4b0b-a249-7fba91d4d3f8"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4877.5" y="2638.75"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s62_sa263" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="4541.0" y="2588.75"/> </glyph> <glyph class="macromolecule" id="s63_sa261" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="50.0" x="4740.0" y="2633.75"/> <glyph class="state variable" id="_3627cf30-a4a5-4135-abca-2858cb7df085"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4735.0" y="2653.75"/> </glyph> <glyph class="unit of information" id="_0af3750e-cd40-440b-9fd5-84ae0b673c55"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4757.5" y="2628.75"/> </glyph> </glyph> <glyph class="complex" id="s65_csa50" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:B2M:MHC class I* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s65"/> <bbox w="180.0" h="70.0" x="4320.0" y="2623.75"/> <glyph class="macromolecule" id="s1833_sa229"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="50.0" x="4330.0" y="2633.75"/> <glyph class="state variable" id="_cb381afb-6764-4a36-92ef-dd04cde02a0b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4325.0" y="2653.75"/> </glyph> <glyph class="unit of information" id="_08f0f510-41a7-4823-95e3-df3c6e956d61"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4347.5" y="2628.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s1834_sa264"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="4415.0" y="2630.0"/> </glyph> </glyph> <glyph class="complex" id="s72_csa52" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CALR:PDIA3 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s72"/> <bbox w="100.0" h="120.0" x="4520.0" y="2733.75"/> <glyph class="macromolecule" id="s1923_sa265"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: protein disulfide isomerase family A member 3 HUGO:PDIA3 hgnc_id:HGNC:4606 HGNC:4606 ENTREZ:2923 UNIPROT:P30101 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 PDIA3(ERp57) is a disulfide isomerase it is a non-covalently associated component of the peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PDIA3"/> <bbox w="80.0" h="40.0" x="4530.0" y="2743.75"/> </glyph> <glyph class="macromolecule" id="s1924_sa266"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: calreticulin HUGO:CALR hgnc_id:HGNC:1455 HGNC:1455 ENTREZ:811 UNIPROT:P27797 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 CALR (CRT or calreticulin) is a lectin specific for monoglucosylated N-linked glycans (17) that binds to the MHC class I molecule via its carbohydrate side chain. It also associates non-covalently with ERp57 in peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting PMID:23157435, PMID:16239148, PMID:20958319 CALR (CRT or calreticulin) is released by dying tumor cells and acts as eat-me signal. It acts via CD91 (LRP1) and initiates clearance of viable or apoptotic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CALR"/> <bbox w="80.0" h="40.0" x="4530.0" y="2793.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s73_sa267" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: endoplasmic reticulum aminopeptidase 1 HUGO:ERAP1 hgnc_id:HGNC:18173 HGNC:18173 ENTREZ:51752 UNIPROT:Q9NZ08 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22790179, PMID:17277129 Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1)) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ERAP1"/> <bbox w="80.0" h="40.0" x="3535.0" y="2210.0"/> </glyph> <glyph class="macromolecule" id="s1816_sa268" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: leucyl and cystinyl aminopeptidase HUGO:LNPEP hgnc_id:HGNC:6656 HGNC:6656 ENTREZ:4012 UNIPROT:Q9UIQ6 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:22790179, PMID:19498108 Proteasome-generated polypeptides need to be trimmed by amino-terminal peptidases to be loaded on MHC class I molecules, and both ER-associated aminopeptidase 1 (ERAP1)6 and endosomal insulin-responsive aminopeptidase (IRAP; also known as cystinyl aminopeptidase)7 have been shown to be involved in cross-presentation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRAP"/> <bbox w="80.0" h="40.0" x="3665.0" y="2250.0"/> </glyph> <glyph class="macromolecule" id="s1053_sa270" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cytochrome b-245 beta chain HUGO:CYBB hgnc_id:HGNC:2578 HGNC:2578 ENTREZ:1536 UNIPROT:P04839 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. PMID:19380816, PMID:21383238 The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). STAT3 upregulates expression of NOX2 subunits, primarily p47(NCF1) and gp91(CYBB) in MDSC, In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CYBB"/> <bbox w="80.0" h="40.0" x="2230.0" y="1600.0"/> </glyph> <glyph class="simple chemical" id="s1057_sa272" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FAD"/> <bbox w="70.0" h="25.0" x="2245.0" y="1717.5"/> </glyph> <glyph class="macromolecule" id="s1050_sa274" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: neutrophil cytosolic factor 1 HUGO:NCF1 hgnc_id:HGNC:7660 HGNC:7660 ENTREZ:653361 UNIPROT:P14598 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. PMID:19380816, PMID:21383238 The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). STAT3 upregulates expression of NOX2 subunits, primarily p47(NCF1) and gp91(CYBB) in MDSC, In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NCF1"/> <bbox w="80.0" h="40.0" x="2330.0" y="1540.0"/> </glyph> <glyph class="complex" id="s1054_csa53" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GTP:RAC1_2* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1054"/> <bbox w="100.0" h="120.0" x="2005.0" y="1661.25"/> <glyph class="macromolecule" id="s1051_sa278"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) HUGO:RAC1 hgnc_id:HGNC:9801 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) HUGO:RAC2 hgnc_id:HGNC:9802 HGNC:9802 ENTREZ:5880 UNIPROT:P15153 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RAC1_2*"/> <bbox w="80.0" h="40.0" x="2015.0" y="1681.25"/> </glyph> <glyph class="simple chemical" id="s1055_sa279"> <label text="GTP"/> <bbox w="70.0" h="25.0" x="2020.0" y="1728.75"/> </glyph> </glyph> <glyph class="complex" id="s1045_csa54" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CYBA:CYBB:FAD:GTP:NCF1:NCF2:NCF4:RAC1_2*:heme Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. The regulation of phagosomal pH exerted by NOX2, and thereby of the efficacy of antigen cross-presentation in DCs, represents a clear illustration of how NOX2 can influence CD8(+) T lymphocyte responses. PMID:22157818 Phagosomal proteolysis in dendritic cells is modulated by NADPH oxidase in a pH-independent manner. PMID:22157818, PMID:22827577 CTSS (cathepsin S), CTSB (cathepsin B) and CTSL (cathepsin L) are active in DC phagosomes. Phagosomal NOX2 activity via ROS inhibits the activities of local cysteine (B/S/L ), but not aspartic (D/E), cathepsins. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NADPH oxidase"/> <bbox w="215.0" h="235.0" x="2022.5" y="1842.5"/> <glyph class="macromolecule" id="s1038_sa280"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: cytochrome b-245 beta chain HUGO:CYBB hgnc_id:HGNC:2578 HGNC:2578 ENTREZ:1536 UNIPROT:P04839 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. PMID:19380816, PMID:21383238 The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). STAT3 upregulates expression of NOX2 subunits, primarily p47(NCF1) and gp91(CYBB) in MDSC, In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CYBB"/> <bbox w="80.0" h="40.0" x="2037.5" y="1847.5"/> </glyph> <glyph class="macromolecule" id="s1039_sa281"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: cytochrome b-245 alpha chain HUGO:CYBA hgnc_id:HGNC:2577 HGNC:2577 ENTREZ:1535 UNIPROT:P13498 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CYBA"/> <bbox w="80.0" h="40.0" x="2037.5" y="1897.5"/> </glyph> <glyph class="macromolecule" id="s1040_sa282"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: neutrophil cytosolic factor 1 HUGO:NCF1 hgnc_id:HGNC:7660 HGNC:7660 ENTREZ:653361 UNIPROT:P14598 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. PMID:19380816, PMID:21383238 The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). STAT3 upregulates expression of NOX2 subunits, primarily p47(NCF1) and gp91(CYBB) in MDSC, In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NCF1"/> <bbox w="80.0" h="40.0" x="2137.5" y="1847.5"/> </glyph> <glyph class="macromolecule" id="s1041_sa283"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: neutrophil cytosolic factor 4 HUGO:NCF4 hgnc_id:HGNC:7662 HGNC:7662 ENTREZ:4689 UNIPROT:Q15080 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NCF4"/> <bbox w="80.0" h="40.0" x="2137.5" y="1897.5"/> </glyph> <glyph class="macromolecule" id="s1042_sa284"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: neutrophil cytosolic factor 2 HUGO:NCF2 hgnc_id:HGNC:7661 HGNC:7661 ENTREZ:4688 UNIPROT:P19878 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NCF2"/> <bbox w="80.0" h="40.0" x="2137.5" y="1947.5"/> </glyph> <glyph class="macromolecule" id="s1043_sa285"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) HUGO:RAC1 hgnc_id:HGNC:9801 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) HUGO:RAC2 hgnc_id:HGNC:9802 HGNC:9802 ENTREZ:5880 UNIPROT:P15153 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RAC1_2*"/> <bbox w="80.0" h="40.0" x="2037.5" y="1947.5"/> </glyph> <glyph class="simple chemical" id="s1044_sa286"> <label text="GTP"/> <bbox w="70.0" h="25.0" x="2042.5" y="1995.0"/> </glyph> <glyph class="simple chemical" id="s1046_sa287"> <label text="heme"/> <bbox w="70.0" h="25.0" x="2092.5" y="2025.0"/> </glyph> <glyph class="simple chemical" id="s1047_sa288"> <label text="FAD"/> <bbox w="70.0" h="25.0" x="2142.5" y="1995.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1818_sa276" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: neutrophil cytosolic factor 2 HUGO:NCF2 hgnc_id:HGNC:7661 HGNC:7661 ENTREZ:4688 UNIPROT:P19878 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NCF2"/> <bbox w="80.0" h="40.0" x="2330.0" y="1670.0"/> </glyph> <glyph class="macromolecule" id="s1819_sa271" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cytochrome b-245 alpha chain HUGO:CYBA hgnc_id:HGNC:2577 HGNC:2577 ENTREZ:1535 UNIPROT:P13498 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CYBA"/> <bbox w="80.0" h="40.0" x="2130.0" y="1600.0"/> </glyph> <glyph class="simple chemical" id="s1820_sa273" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="heme"/> <bbox w="70.0" h="25.0" x="2175.0" y="1717.5"/> </glyph> <glyph class="macromolecule" id="s1821_sa275" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: neutrophil cytosolic factor 4 HUGO:NCF4 hgnc_id:HGNC:7662 HGNC:7662 ENTREZ:4689 UNIPROT:Q15080 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NCF4"/> <bbox w="80.0" h="40.0" x="2330.0" y="1600.0"/> </glyph> <glyph class="complex" id="s1822_csa55" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TAP1:TAP2:TAPASIN* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:16181333 Antigen peptides are transported into the ER from the cytosol via TAPs, tapasin stabilizes the TAP1/TAP2 heterodimer. PMID:22790179 TAPs re-importe processed antigens from cytosole to phagosome References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s55"/> <bbox w="100.0" h="180.0" x="2860.0" y="1590.0"/> <glyph class="macromolecule" id="s28_sa289"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: transporter 1, ATP binding cassette subfamily B member HUGO:TAP1 hgnc_id:HGNC:43 HGNC:43 ENTREZ:6890 UNIPROT:Q03518 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Antigen peptides are transported into the ER from the cytosol via TAPs PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting. TAP-mediates peptide transport and loading on MHC class I in purified phagosomes. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAP1"/> <bbox w="80.0" h="40.0" x="2870.0" y="1650.0"/> </glyph> <glyph class="macromolecule" id="s29_sa290"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: transporter 2, ATP binding cassette subfamily B member HUGO:TAP2 hgnc_id:HGNC:44 HGNC:44 ENTREZ:6891 UNIPROT:Q03519 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Antigen peptides are transported into the ER from the cytosol via TAPs, tapasin stabilizes the TAP1/TAP2 heterodimer. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. TAP-mediates peptide transport and loading on MHC class I in purified phagosomes. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAP2"/> <bbox w="80.0" h="40.0" x="2870.0" y="1700.0"/> </glyph> <glyph class="macromolecule" id="s34_sa291"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TAP binding protein HUGO:TAPBP hgnc_id:HGNC:11566 HGNC:11566 ENTREZ:6892 UNIPROT:O15533 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333 Tapasin stabilizes the TAP1/TAP2 heterodimer PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation. PMID:10973281 Tapasin may have a quantitative effect on the peptide loading process as suggested by the impaired antigen presentation by DCs from Tpn-/- mice. dendritic cells of tapasin-deficient mice do not cross-present protein antigen via the MHC class I pathway. PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAPASIN*"/> <bbox w="80.0" h="40.0" x="2870.0" y="1600.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1827_sa293" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: syntaxin 4 HUGO:STX4 hgnc_id:HGNC:11439 HGNC:11439 ENTREZ:6810 UNIPROT:Q12846 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:22790179 The SNARE SEC22B, which localizes in the ER–Golgi intermediate compartment (ERGIC) and interacts with syntaxin 4 on phagosomes, mediates the recruitment of a subset of ER components, including transporter associated with antigen processing (TAP), to phagosomes. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STX4"/> <bbox w="80.0" h="40.0" x="2985.0" y="1911.25"/> </glyph> <glyph class="complex" id="s1828_csa56" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:B2M:MHC class I* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s65"/> <bbox w="180.0" h="70.0" x="2470.0" y="1465.0"/> <glyph class="macromolecule" id="s67_sa294"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="50.0" x="2480.0" y="1475.0"/> <glyph class="state variable" id="_c2412838-e240-487b-a831-dc76bcecbb0b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2475.0" y="1495.0"/> </glyph> <glyph class="unit of information" id="_9e2211e5-6417-4842-9e65-869594ab1e37"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2497.5" y="1470.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s66_sa295"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="2560.0" y="1475.0"/> </glyph> </glyph> <glyph class="complex" id="s1829_csa57" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:B2M:MHC class I*:Tumor_antigen_fragment Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:11154916, PMID:11509172 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s35"/> <bbox w="200.0" h="125.0" x="2630.0" y="1557.5"/> <glyph class="macromolecule" id="s54_sa296"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="50.0" x="2650.0" y="1612.5"/> <glyph class="state variable" id="_2b2c4c56-c3ea-4841-a2e8-11599f2e9ed8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2645.0" y="1632.5"/> </glyph> <glyph class="unit of information" id="_3c4bad86-add5-4ce3-9f2c-52e640e77ef4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2667.5" y="1607.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s53_sa297"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="2650.0" y="1567.5"/> <glyph class="unit of information" id="_1b22c857-58f4-45f0-9b22-9dfd743766ad"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="2665.0" y="1562.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s56_sa298"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="2740.0" y="1612.5"/> </glyph> </glyph> <glyph class="complex" id="s1836_csa58" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MHC class II*:Tumor_antigen_fragment Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s17"/> <bbox w="120.0" h="140.0" x="3965.0" y="3620.0"/> <glyph class="macromolecule" id="s15_sa300"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="3985.0" y="3700.0"/> <glyph class="state variable" id="_53e30076-e332-4e5a-b55e-1802a7c23b34"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3980.0" y="3715.0"/> </glyph> <glyph class="unit of information" id="_a8ebd384-0ed7-4c78-b3e9-f841e83a3b2b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4002.5" y="3695.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s21_sa301"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="3985.0" y="3640.0"/> <glyph class="unit of information" id="_9cc978db-7834-4700-adda-e97fd90e485b"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4000.0" y="3635.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s1839_sa302" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 CD1b molecule HUGO:CD1B hgnc_id:HGNC:1635 HGNC:1635 ENTREZ:910 UNIPROT:P29016 CD1c molecule HUGO:CD1C hgnc_id:HGNC:1636 HGNC:1636 ENTREZ:911 UNIPROT:P29017 CD1d molecule HUGO:CD1D hgnc_id:HGNC:1637 HGNC:1637 ENTREZ:912 UNIPROT:P15813 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:10837075, PMID:10358761, PMID:12391186 CD1 family as nonclassical, Ag-presenting molecules involved in regulation of T cell responses to microbial lipids and glycolipids-containing Ag. Both endogenous and exogenous lipids can be presented, and this pathway may contribute not only to microbial immunity but to autoimmunity and antitumor responses. In humans, four CD1 proteins (CD1a–d) are expressed by myeloid DCs, whereas in mice only CD1d has been identified. CD1 proteins are functionally heterogeneous, and two subgroups can be identified. Subgroup I, including human CD1b–c, can present glycolipids to a large repertoire of T cells. Indeed, mycobacteria-specific, CD1b-restricted CD8+α/β TCR T cells have been demonstrated. Binding of the lipids to these CD1 molecules requires endosomal acidification. Subgroup II includes mouse and human CD1d and binds a limited set of Ags (α-galactosyloceramide) and activates a restricted set of T cells as well as NK T cells PMID:10190903 Alpha-galactosylceramide (alpha-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12-mediated antitumor activities. Production of IFN-gamma by NKT cells in response to alpha-GalCer required IL-12 produced by dendritic cells (DCs) and direct contact between NKT cells and DCs through CD40/CD40 ligand interactions. Moreover, alpha-GalCer strongly induced the expression of IL-12 receptor on NKT cells from wild-type but not CD1(-/-) or Valpha14(-/-) mice. PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25582338 CD1a, which is involved in lipid Ag presentation, was significantly lower on imIL-15 DCs and mIL-15 DCs than on IL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1*"/> <bbox w="80.0" h="40.0" x="2315.0" y="2075.0"/> <glyph class="unit of information" id="_4ac2e657-3b57-46f8-9d22-811c638f1489"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2332.5" y="2070.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1840_sa303" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="2465.0" y="2105.0"/> </glyph> <glyph class="simple chemical" id="s1841_sa304"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Lipid_antigen"/> <bbox w="115.0" h="42.5" x="3962.5" y="4223.75"/> </glyph> <glyph class="complex" id="s1842_csa59" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:B2M:CD1*:Lipid_antigen Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10358761 CD1 family proteins are nonclassical (lipid), Ag-presenting molecules All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1842"/> <bbox w="190.0" h="130.0" x="2370.0" y="2235.0"/> <glyph class="simple chemical" id="s1848_sa306"> <label text="Lipid_antigen"/> <bbox w="115.0" h="42.5" x="2372.5" y="2243.75"/> </glyph> <glyph class="macromolecule" id="s1849_sa307"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 CD1b molecule HUGO:CD1B hgnc_id:HGNC:1635 HGNC:1635 ENTREZ:910 UNIPROT:P29016 CD1c molecule HUGO:CD1C hgnc_id:HGNC:1636 HGNC:1636 ENTREZ:911 UNIPROT:P29017 CD1d molecule HUGO:CD1D hgnc_id:HGNC:1637 HGNC:1637 ENTREZ:912 UNIPROT:P15813 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:10837075, PMID:10358761, PMID:12391186 CD1 family as nonclassical, Ag-presenting molecules involved in regulation of T cell responses to microbial lipids and glycolipids-containing Ag. Both endogenous and exogenous lipids can be presented, and this pathway may contribute not only to microbial immunity but to autoimmunity and antitumor responses. In humans, four CD1 proteins (CD1a–d) are expressed by myeloid DCs, whereas in mice only CD1d has been identified. CD1 proteins are functionally heterogeneous, and two subgroups can be identified. Subgroup I, including human CD1b–c, can present glycolipids to a large repertoire of T cells. Indeed, mycobacteria-specific, CD1b-restricted CD8+α/β TCR T cells have been demonstrated. Binding of the lipids to these CD1 molecules requires endosomal acidification. Subgroup II includes mouse and human CD1d and binds a limited set of Ags (α-galactosyloceramide) and activates a restricted set of T cells as well as NK T cells PMID:10190903 Alpha-galactosylceramide (alpha-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12-mediated antitumor activities. Production of IFN-gamma by NKT cells in response to alpha-GalCer required IL-12 produced by dendritic cells (DCs) and direct contact between NKT cells and DCs through CD40/CD40 ligand interactions. Moreover, alpha-GalCer strongly induced the expression of IL-12 receptor on NKT cells from wild-type but not CD1(-/-) or Valpha14(-/-) mice. PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25582338 CD1a, which is involved in lipid Ag presentation, was significantly lower on imIL-15 DCs and mIL-15 DCs than on IL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1*"/> <bbox w="80.0" h="40.0" x="2380.0" y="2295.0"/> <glyph class="unit of information" id="_72fc603c-5dca-4ef8-adde-c61e4013f21d"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2397.5" y="2290.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1850_sa308"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="2470.0" y="2295.0"/> </glyph> </glyph> <glyph class="simple chemical" id="s1843_sa305" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Lipid_antigen"/> <bbox w="115.0" h="42.5" x="2227.5" y="2123.75"/> </glyph> <glyph class="complex" id="s1847_csa60" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:B2M:CD1*:Lipid_antigen Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1842"/> <bbox w="195.0" h="125.0" x="3737.5" y="3637.5"/> <glyph class="simple chemical" id="s1844_sa309"> <label text="Lipid_antigen"/> <bbox w="115.0" h="42.5" x="3745.0" y="3646.25"/> </glyph> <glyph class="macromolecule" id="s1845_sa310"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 CD1b molecule HUGO:CD1B hgnc_id:HGNC:1635 HGNC:1635 ENTREZ:910 UNIPROT:P29016 CD1c molecule HUGO:CD1C hgnc_id:HGNC:1636 HGNC:1636 ENTREZ:911 UNIPROT:P29017 CD1d molecule HUGO:CD1D hgnc_id:HGNC:1637 HGNC:1637 ENTREZ:912 UNIPROT:P15813 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:10837075, PMID:10358761, PMID:12391186 CD1 family as nonclassical, Ag-presenting molecules involved in regulation of T cell responses to microbial lipids and glycolipids-containing Ag. Both endogenous and exogenous lipids can be presented, and this pathway may contribute not only to microbial immunity but to autoimmunity and antitumor responses. In humans, four CD1 proteins (CD1a–d) are expressed by myeloid DCs, whereas in mice only CD1d has been identified. CD1 proteins are functionally heterogeneous, and two subgroups can be identified. Subgroup I, including human CD1b–c, can present glycolipids to a large repertoire of T cells. Indeed, mycobacteria-specific, CD1b-restricted CD8+α/β TCR T cells have been demonstrated. Binding of the lipids to these CD1 molecules requires endosomal acidification. Subgroup II includes mouse and human CD1d and binds a limited set of Ags (α-galactosyloceramide) and activates a restricted set of T cells as well as NK T cells PMID:10190903 Alpha-galactosylceramide (alpha-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12-mediated antitumor activities. Production of IFN-gamma by NKT cells in response to alpha-GalCer required IL-12 produced by dendritic cells (DCs) and direct contact between NKT cells and DCs through CD40/CD40 ligand interactions. Moreover, alpha-GalCer strongly induced the expression of IL-12 receptor on NKT cells from wild-type but not CD1(-/-) or Valpha14(-/-) mice. PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25582338 CD1a, which is involved in lipid Ag presentation, was significantly lower on imIL-15 DCs and mIL-15 DCs than on IL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1*"/> <bbox w="80.0" h="40.0" x="3757.5" y="3692.5"/> <glyph class="unit of information" id="_292a863e-3893-41ad-a649-c1919b00bf35"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3775.0" y="3687.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1846_sa311"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: beta-2-microglobulin HUGO:B2M hgnc_id:HGNC:914 HGNC:914 ENTREZ:567 UNIPROT:P61769 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:10358761 All CD1 proteins studied to date are expressed on the surface of cells as type I transmembrane proteins that associate noncovalently with β2-microglobulin PMID:11717192 The gene expression of TAP1, TAP2, tapasin, β2m and HLA-α HC is up-regulated in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B2M"/> <bbox w="80.0" h="40.0" x="3847.5" y="3692.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s760_sa1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:11238627 TNF induces p38 signaling and downstream expression of CD1a, CD40, CD80, CD86, HLA-DR, and CD83 References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: tumor necrosis factor HUGO:TNF hgnc_id:HGNC:11892 HGNC:11892 ENTREZ:7124 UNIPROT:P01375 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12391186 Maturation of monocyte-derived DCs was induced by TNF-α The surface levels of MHC class II increased markedly after TNF-α stimulation on CD83+ DC In contrast to the striking increase in surface expression of MHC class II, the cell surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:12928370 TNF, but not IL-1, induce monocytes to become DCs despite the presence of fibroblasts. TNF converts activated monocytes/early Mφ into DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNF"/> <bbox w="80.0" h="40.0" x="5335.0" y="305.0"/> </glyph> <glyph class="macromolecule" id="s1851_sa312" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cathepsin B HUGO:CTSB hgnc_id:HGNC:2527 HGNC:2527 ENTREZ:1508 UNIPROT:P07858 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:22157818 CTSS (cathepsin S), CTSB (cathepsin B) and CTSL (cathepsin L) are active in DC phagosomes. Phagosomal NOX2 activity via ROS inhibits the activities of local cysteine (B/S/L ), but not aspartic (D/E), cathepsins. PMID:12776207 Cathepsins B,D,L, S and AEP (LGMN) are the lysosomal proteases implicated in antigen presentation in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CTSB"/> <bbox w="80.0" h="40.0" x="2515.0" y="2050.0"/> </glyph> <glyph class="simple chemical" id="s353_sa313" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="O2"/> <bbox w="70.0" h="25.0" x="2265.0" y="1817.5"/> </glyph> <glyph class="simple chemical" id="s377_sa314" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:19372727 The enzyme responsible for O2•- production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="O2-"/> <bbox w="70.0" h="25.0" x="2262.0" y="1906.5"/> </glyph> <glyph class="simple chemical" id="s375_sa315" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="H2O2"/> <bbox w="70.0" h="25.0" x="2355.0" y="1907.5"/> </glyph> <glyph class="simple chemical" id="s378_sa316" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="hydroxyl"/> <bbox w="70.0" h="25.0" x="2355.0" y="1817.5"/> </glyph> <glyph class="macromolecule" id="s1852_sa317" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cathepsin D HUGO:CTSD hgnc_id:HGNC:2529 HGNC:2529 ENTREZ:1509 UNIPROT:P07339 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16237087 CTSD (aspartic cathepsin D) and CTSG (cathepsin G) participate in antigen processing in DC. PMID:12776207 Cathepsins B,D,L, S and AEP (LGMN) are the lysosomal proteases implicated in antigen presentation in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CTSD"/> <bbox w="80.0" h="40.0" x="2515.0" y="1950.0"/> </glyph> <glyph class="macromolecule" id="s1853_sa318" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cathepsin G HUGO:CTSG hgnc_id:HGNC:2532 HGNC:2532 ENTREZ:1511 UNIPROT:P08311 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16237087 CTSD (aspartic cathepsin D) and CTSG (cathepsin G) participate in antigen processing in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CTSG"/> <bbox w="80.0" h="40.0" x="2515.0" y="2000.0"/> </glyph> <glyph class="macromolecule" id="s1855_sa320" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:10716924, PMID:10611337, PMID:22138314 Dendritic cells carry functional HLA-DM on the surface, which is down-regulated upon maturation. CLIP which blocks peptide binding until HLA-DM binds to MHC II, releasing CLIP and allowing other (antigen) peptides to bind. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="HLA-DM* "/> <bbox w="80.0" h="50.0" x="2895.0" y="2255.0"/> <glyph class="unit of information" id="_105ff6ae-dde2-4cb1-8cf4-be0d581acb59"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2912.5" y="2250.0"/> </glyph> </glyph> <glyph class="complex" id="s1856_csa61" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CD74:MHC class II* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22076556 The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1856"/> <bbox w="100.0" h="120.0" x="3795.0" y="2600.0"/> <glyph class="macromolecule" id="s1859_sa321"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD74 molecule HUGO:CD74 hgnc_id:HGNC:1697 HGNC:1697 ENTREZ:972 UNIPROT:P04233 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181339 Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD74"/> <bbox w="80.0" h="40.0" x="3805.0" y="2610.0"/> </glyph> <glyph class="macromolecule" id="s1871_sa330"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="3805.0" y="2655.0"/> <glyph class="state variable" id="_3cbf18a4-f64a-4f49-9d0d-4ba92287d365"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3800.0" y="2670.0"/> </glyph> <glyph class="unit of information" id="_56797fef-e1bd-4729-b677-0014cf076bf5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3822.5" y="2650.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s1858_csa62" compartmentRef="c9_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CD74:MHC class II* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22076556, PMID:10631952, PMID:22138314, PMID:10611337 The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1856"/> <bbox w="100.0" h="120.0" x="3125.0" y="2071.25"/> <glyph class="macromolecule" id="s1862_sa322"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD74 molecule HUGO:CD74 hgnc_id:HGNC:1697 HGNC:1697 ENTREZ:972 UNIPROT:P04233 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181339 Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD74"/> <bbox w="80.0" h="40.0" x="3135.0" y="2081.25"/> </glyph> <glyph class="macromolecule" id="s1863_sa323"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="3135.0" y="2131.25"/> <glyph class="state variable" id="_fff5e1e0-9d19-46d6-b698-50be7b95d2c4"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3130.0" y="2146.25"/> </glyph> <glyph class="unit of information" id="_b5cfc333-ce94-4376-94ae-ffd581911f5a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3152.5" y="2126.25"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s1861_csa63" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CLIP:MHC class II* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22076556 The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1856"/> <bbox w="100.0" h="120.0" x="3015.0" y="2261.25"/> <glyph class="macromolecule" id="s26_sa325"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="3025.0" y="2321.25"/> <glyph class="state variable" id="_575b49fd-abc6-4688-8842-b5584a6540c6"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3020.0" y="2336.25"/> </glyph> <glyph class="unit of information" id="_07bbe57d-0c28-4896-9700-a95020adaaee"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3042.5" y="2316.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s1864_sa326"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD74 molecule HUGO:CD74 hgnc_id:HGNC:1697 HGNC:1697 ENTREZ:972 UNIPROT:P04233 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181339 Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CLIP"/> <bbox w="80.0" h="40.0" x="3025.0" y="2271.25"/> <glyph class="unit of information" id="_c583702d-22ca-4ce8-a936-f658ef057e3e"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="3040.0" y="2266.25"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s1865_sa327" compartmentRef="c9_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD74 molecule HUGO:CD74 hgnc_id:HGNC:1697 HGNC:1697 ENTREZ:972 UNIPROT:P04233 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181339 Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CLIP"/> <bbox w="80.0" h="40.0" x="2885.0" y="2420.0"/> <glyph class="unit of information" id="_d7c20b00-0ac9-4418-92c9-3a4ea4b1997e"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="2900.0" y="2415.0"/> </glyph> </glyph> <glyph class="complex" id="s1867_csa65" compartmentRef="c9_ca9"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MHC class II*:Tumor_antigen_fragment Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22076556 The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s17"/> <bbox w="100.0" h="130.0" x="2695.0" y="2466.25"/> <glyph class="macromolecule" id="s1868_sa328"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="2705.0" y="2526.25"/> <glyph class="state variable" id="_0137c786-b56c-4452-bda3-c7a082facc56"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2700.0" y="2541.25"/> </glyph> <glyph class="unit of information" id="_d7094b49-0fb1-4687-9009-b7d1bd4e1ef4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2722.5" y="2521.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s1869_sa329"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="2705.0" y="2476.25"/> <glyph class="unit of information" id="_f77864b6-c4dd-4ed4-92d1-8819070bcd0f"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="2720.0" y="2471.25"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s1870_sa319" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="2775.0" y="2270.0"/> <glyph class="state variable" id="_a66682e4-f1e3-4980-ba6e-bdbc2e10c5d4"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2770.0" y="2285.0"/> </glyph> <glyph class="unit of information" id="_bd5f9f30-1af8-4794-9bac-b8ca99623699"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2792.5" y="2265.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1872_sa331" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: myosin IE HUGO:MYO1E hgnc_id:HGNC:7599 HGNC:7599 ENTREZ:4643 UNIPROT:Q12965 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MYO1E"/> <bbox w="80.0" h="40.0" x="2855.0" y="2668.75"/> </glyph> <glyph class="macromolecule" id="s1875_sa334" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: ADP ribosylation factor like GTPase 8B HUGO:ARL8B hgnc_id:HGNC:25564 HGNC:25564 ENTREZ:55207 UNIPROT:Q9NVJ2 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:25637027 MHC Class II Presentation Is Controlled by the Lysosomal Small GTPase, Arl8b Arl8b-silenced cells show reduced formation of MHC II–peptide complexes in lysosomes. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARL8B"/> <bbox w="80.0" h="40.0" x="2655.0" y="2280.0"/> </glyph> <glyph class="macromolecule" id="s1876_sa335" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: pleckstrin and Sec7 domain containing 4 HUGO:PSD4 hgnc_id:HGNC:19096 HGNC:19096 ENTREZ:23550 UNIPROT:Q8NDX1 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 PSD4 is selectively expressed in the immune system and promotes GTP loading of ARL14/ARF7. Probably downstream of PIP5K1A. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PSD4"/> <clone/> <bbox w="80.0" h="40.0" x="3295.0" y="2868.75"/> </glyph> <glyph class="macromolecule" id="s1876_sa345" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: pleckstrin and Sec7 domain containing 4 HUGO:PSD4 hgnc_id:HGNC:19096 HGNC:19096 ENTREZ:23550 UNIPROT:Q8NDX1 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 PSD4 is selectively expressed in the immune system and promotes GTP loading of ARL14/ARF7. Probably downstream of PIP5K1A. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PSD4"/> <clone/> <bbox w="80.0" h="40.0" x="3425.0" y="2868.75"/> </glyph> <glyph class="complex" id="s1877_csa66" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ARL14:GDP Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:21458045 PSD4 is selectively expressed in the immune system and promotes GTP loading of ARL14/ARF7. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1877"/> <bbox w="100.0" h="120.0" x="3285.0" y="2660.0"/> <glyph class="macromolecule" id="s1881_sa333"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ADP ribosylation factor like GTPase 14 HUGO:ARL14 hgnc_id:HGNC:22974 HGNC:22974 ENTREZ:80117 UNIPROT:Q8N4G2 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARL14"/> <bbox w="80.0" h="40.0" x="3295.0" y="2710.0"/> </glyph> <glyph class="simple chemical" id="s1882_sa337"> <label text="GDP"/> <bbox w="70.0" h="25.0" x="3300.0" y="2677.5"/> </glyph> </glyph> <glyph class="simple chemical" id="s1878_sa336" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GDP"/> <clone/> <bbox w="70.0" h="25.0" x="3180.0" y="2616.25"/> </glyph> <glyph class="simple chemical" id="s1878_sa368" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GDP"/> <clone/> <bbox w="62.5" h="26.25" x="2783.75" y="3176.875"/> </glyph> <glyph class="simple chemical" id="s1878_sa485" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GDP"/> <clone/> <bbox w="62.5" h="26.25" x="3423.75" y="1456.875"/> </glyph> <glyph class="complex" id="s1883_csa67" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ARL14:GTP Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:21458045 PSD4 is selectively expressed in the immune system and promotes GTP loading of ARL14/ARF7. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1877"/> <bbox w="100.0" h="120.0" x="3125.0" y="2658.75"/> <glyph class="macromolecule" id="s1884_sa338"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ADP ribosylation factor like GTPase 14 HUGO:ARL14 hgnc_id:HGNC:22974 HGNC:22974 ENTREZ:80117 UNIPROT:Q8N4G2 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARL14"/> <bbox w="80.0" h="40.0" x="3135.0" y="2708.75"/> </glyph> <glyph class="simple chemical" id="s1885_sa340"> <label text="GTP"/> <bbox w="70.0" h="25.0" x="3140.0" y="2676.25"/> </glyph> </glyph> <glyph class="simple chemical" id="s1886_sa341" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GTP"/> <clone/> <bbox w="70.0" h="25.0" x="3260.0" y="2616.25"/> </glyph> <glyph class="simple chemical" id="s1886_sa369" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GTP"/> <clone/> <bbox w="70.0" h="25.0" x="2870.0" y="3177.5"/> </glyph> <glyph class="simple chemical" id="s1886_sa484" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GTP"/> <clone/> <bbox w="70.0" h="25.0" x="3510.0" y="1457.5"/> </glyph> <glyph class="macromolecule" id="s1887_sa342" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: phosphatidylinositol-4-phosphate 5-kinase type 1 alpha HUGO:PIP5K1A hgnc_id:HGNC:8994 HGNC:8994 ENTREZ:8394 UNIPROT:Q99755 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 PSD4 is selectively expressed in the immune system and promotes GTP loading of ARL14/ARF7. Probably downstream of PIP5K1A. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PIP5K1A"/> <bbox w="80.0" h="40.0" x="3485.0" y="2728.75"/> </glyph> <glyph class="simple chemical" id="s1866_sa343" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:15817676 PIP2 is mainly synthesized by the phosphorylation of phosphatidylinositol4-phosphate (PI4P) at the D-5 position of the inositol ring by phosphatidylinositol4phosphate 5-kinase type I (PI5KI) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PtdIns(4)-P"/> <clone/> <bbox w="70.0" h="25.0" x="3550.0" y="2806.25"/> </glyph> <glyph class="simple chemical" id="s1866_sa478" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:15817676 PIP2 is mainly synthesized by the phosphorylation of phosphatidylinositol4-phosphate (PI4P) at the D-5 position of the inositol ring by phosphatidylinositol4phosphate 5-kinase type I (PI5KI) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PtdIns(4)-P"/> <clone/> <bbox w="70.0" h="25.0" x="3540.0" y="1706.25"/> </glyph> <glyph class="simple chemical" id="s744_sa344" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:12040186 The activated PI3K converts the plasma membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3]. PMID:12393695 SHIP1 inhinits NK cells activation via bloking of PI3K pathway. It hydrolyzes the 5′-phosphate of PI3,4,5P3l eading to its conversion to PI3,4P2. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PIP2*"/> <clone/> <bbox w="70.0" h="25.0" x="3430.0" y="2806.25"/> </glyph> <glyph class="simple chemical" id="s744_sa479" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:12040186 The activated PI3K converts the plasma membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3]. PMID:12393695 SHIP1 inhinits NK cells activation via bloking of PI3K pathway. It hydrolyzes the 5′-phosphate of PI3,4,5P3l eading to its conversion to PI3,4P2. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PIP2*"/> <clone/> <bbox w="70.0" h="25.0" x="3675.0" y="1706.25"/> </glyph> <glyph class="complex" id="s1888_csa69" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ARL14:ARL14EP:GTP:MYO1E Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1888"/> <bbox w="180.0" h="140.0" x="2915.0" y="2728.75"/> <glyph class="macromolecule" id="s1873_sa332"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ADP ribosylation factor like GTPase 14 effector protein HUGO:ARL14EP hgnc_id:HGNC:26798 HGNC:26798 ENTREZ:120534 UNIPROT:Q8N8R7 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARL14EP"/> <bbox w="80.0" h="40.0" x="2925.0" y="2788.75"/> </glyph> <glyph class="simple chemical" id="s1890_sa348"> <label text="GTP"/> <bbox w="70.0" h="25.0" x="3010.0" y="2756.25"/> </glyph> <glyph class="macromolecule" id="s1889_sa349"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ADP ribosylation factor like GTPase 14 HUGO:ARL14 hgnc_id:HGNC:22974 HGNC:22974 ENTREZ:80117 UNIPROT:Q8N4G2 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARL14"/> <bbox w="80.0" h="40.0" x="3005.0" y="2788.75"/> </glyph> <glyph class="macromolecule" id="s1891_sa350"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: myosin IE HUGO:MYO1E hgnc_id:HGNC:7599 HGNC:7599 ENTREZ:4643 UNIPROT:Q12965 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MYO1E"/> <bbox w="80.0" h="40.0" x="2925.0" y="2738.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s1892_sa351" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: ADP ribosylation factor like GTPase 14 effector protein HUGO:ARL14EP hgnc_id:HGNC:26798 HGNC:26798 ENTREZ:120534 UNIPROT:Q8N8R7 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:21458045 MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP. This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARL14EP"/> <bbox w="80.0" h="40.0" x="2975.0" y="2570.0"/> </glyph> <glyph class="macromolecule" id="s1895_sa755" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: actin beta HUGO:ACTB hgnc_id:HGNC:132 HGNC:132 ENTREZ:60 UNIPROT:P60709 actin gamma 1 HUGO:ACTG1 hgnc_id:HGNC:144 HGNC:144 ENTREZ:71 UNIPROT:P63261 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:18802007 Disruption of actin polymerization inhibits the up-regulation of surface MHCII in a dose-dependent manner in DC. PMID:11766992 Fractalkine via CX3CR1 induces chemotaxis and migration associated actin polymerization in immature as well as in mature DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Actin cytoskeletal*"/> <bbox w="130.0" h="50.0" x="2420.0" y="2755.0"/> </glyph> <glyph class="macromolecule" id="s1896_sa355" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: SWAP switching B-cell complex subunit 70 HUGO:SWAP70 hgnc_id:HGNC:17070 HGNC:17070 ENTREZ:23075 UNIPROT:Q9UH65 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:18802007 SWAP-70 provides in the up-regulation of MHCII surface localization on DCs. SWAP-70 interacts with active Rac1 and RhoA in DC extracts Contrasting positive regulation of Rac, SWAP-70 negatively regulates RhoA and—indirectly—RhoB, References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SWAP70"/> <bbox w="80.0" h="40.0" x="3185.0" y="2870.0"/> </glyph> <glyph class="macromolecule" id="s1897_sa356" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Rho/Rac guanine nucleotide exchange factor 2 HUGO:ARHGEF2 hgnc_id:HGNC:682 HGNC:682 ENTREZ:9181 UNIPROT:Q92974 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16917499 TIKAM1(TRIF) is an adaptor of TLR signaling, TLR signaling via ARHGEF2 (GEFH1)and RHOB regulates MHCII surface expression. Just TRIF-dependent but Myd88-independent pathway enhanced the RhoB activity in DC after LPS stimulation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARHGEF2"/> <clone/> <bbox w="80.0" h="40.0" x="2655.0" y="2790.0"/> </glyph> <glyph class="macromolecule" id="s1897_sa705" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Rho/Rac guanine nucleotide exchange factor 2 HUGO:ARHGEF2 hgnc_id:HGNC:682 HGNC:682 ENTREZ:9181 UNIPROT:Q92974 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16917499 TIKAM1(TRIF) is an adaptor of TLR signaling, TLR signaling via ARHGEF2 (GEFH1)and RHOB regulates MHCII surface expression. Just TRIF-dependent but Myd88-independent pathway enhanced the RhoB activity in DC after LPS stimulation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ARHGEF2"/> <clone/> <bbox w="80.0" h="40.0" x="2655.0" y="2681.25"/> </glyph> <glyph class="complex" id="s1906_csa70" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GDP:RHOB Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1906"/> <bbox w="100.0" h="120.0" x="2795.0" y="2898.75"/> <glyph class="macromolecule" id="s1908_sa353"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ras homolog family member B HUGO:RHOB hgnc_id:HGNC:668 HGNC:668 ENTREZ:388 UNIPROT:P62745 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16917499 TIKAM1(TRIF) is an adaptor of TLR signaling, TLR signaling via ARHGEF2 (GEFH1)and RHOB regulates MHCII surface expression References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RHOB"/> <bbox w="80.0" h="40.0" x="2805.0" y="2908.75"/> </glyph> <glyph class="simple chemical" id="s1907_sa357"> <label text="GDP"/> <bbox w="70.0" h="25.0" x="2810.0" y="2956.25"/> </glyph> </glyph> <glyph class="complex" id="s1909_csa71" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GTP:RHOB Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1909"/> <bbox w="100.0" h="120.0" x="2985.0" y="2898.75"/> <glyph class="simple chemical" id="s1910_sa360"> <label text="GTP"/> <bbox w="70.0" h="25.0" x="3000.0" y="2956.25"/> </glyph> <glyph class="macromolecule" id="s1920_sa365"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ras homolog family member B HUGO:RHOB hgnc_id:HGNC:668 HGNC:668 ENTREZ:388 UNIPROT:P62745 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16917499 TIKAM1(TRIF) is an adaptor of TLR signaling, TLR signaling via ARHGEF2 (GEFH1)and RHOB regulates MHCII surface expression References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RHOB"/> <bbox w="80.0" h="40.0" x="2995.0" y="2908.75"/> </glyph> </glyph> <glyph class="complex" id="s97_csa74" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GTP:RAC1 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s94"/> <bbox w="90.0" h="105.0" x="2720.0" y="3057.5"/> <glyph class="macromolecule" id="s98_sa370"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) HUGO:RAC1 hgnc_id:HGNC:9801 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:14697347, PMID:11146654 The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells by DCs.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RAC1"/> <bbox w="80.0" h="40.0" x="2725.0" y="3060.0"/> </glyph> <glyph class="simple chemical" id="s99_sa371"> <label text="GTP"/> <bbox w="70.0" h="25.0" x="2730.0" y="3107.5"/> </glyph> </glyph> <glyph class="complex" id="s94_csa75" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GDP:RAC1 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s94"/> <bbox w="100.0" h="110.0" x="2905.0" y="3055.0"/> <glyph class="macromolecule" id="s95_sa372"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) HUGO:RAC1 hgnc_id:HGNC:9801 HGNC:9801 ENTREZ:5879 UNIPROT:P63000 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:14697347, PMID:11146654 The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells by DCs.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RAC1"/> <bbox w="80.0" h="40.0" x="2915.0" y="3062.5"/> </glyph> <glyph class="simple chemical" id="s1917_sa373"> <label text="GDP"/> <bbox w="62.5" h="26.25" x="2923.75" y="3106.875"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="s1918_sa754" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: actin beta HUGO:ACTB hgnc_id:HGNC:132 HGNC:132 ENTREZ:60 UNIPROT:P60709 actin gamma 1 HUGO:ACTG1 hgnc_id:HGNC:144 HGNC:144 ENTREZ:71 UNIPROT:P63261 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:18802007 Disruption of actin polymerization inhibits the up-regulation of surface MHCII in a dose-dependent manner in DC. PMID:11766992 Fractalkine via CX3CR1 induces chemotaxis and migration associated actin polymerization in immature as well as in mature DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Actin cytoskeletal*"/> <bbox w="136.0" h="56.0" x="2417.0" y="2862.0"/> <glyph class="unit of information" id="_5ca65d9a-5552-45f6-bb85-9bd9dd4cd2ce"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="2475.0" y="2857.0"/> </glyph> </glyph> <glyph class="complex" id="s1922_csa76" compartmentRef="c6_ca6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CALR:PDIA3 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s72"/> <bbox w="100.0" h="120.0" x="2465.0" y="1650.0"/> <glyph class="macromolecule" id="s69_sa375"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: protein disulfide isomerase family A member 3 HUGO:PDIA3 hgnc_id:HGNC:4606 HGNC:4606 ENTREZ:2923 UNIPROT:P30101 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 PDIA3(ERp57) is a disulfide isomerase it is a non-covalently associated component of the peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PDIA3"/> <bbox w="80.0" h="40.0" x="2475.0" y="1660.0"/> </glyph> <glyph class="macromolecule" id="s71_sa376"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: calreticulin HUGO:CALR hgnc_id:HGNC:1455 HGNC:1455 ENTREZ:811 UNIPROT:P27797 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 CALR (CRT or calreticulin) is a lectin specific for monoglucosylated N-linked glycans (17) that binds to the MHC class I molecule via its carbohydrate side chain. It also associates non-covalently with ERp57 in peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting PMID:23157435, PMID:16239148, PMID:20958319 CALR (CRT or calreticulin) is released by dying tumor cells and acts as eat-me signal. It acts via CD91 (LRP1) and initiates clearance of viable or apoptotic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CALR"/> <bbox w="80.0" h="40.0" x="2475.0" y="1710.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s61_sa262" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: calnexin HUGO:CANX hgnc_id:HGNC:1473 HGNC:1473 ENTREZ:821 UNIPROT:P27824 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CANX"/> <clone/> <bbox w="80.0" h="40.0" x="4740.0" y="2723.75"/> </glyph> <glyph class="macromolecule" id="s61_sa895" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: calnexin HUGO:CANX hgnc_id:HGNC:1473 HGNC:1473 ENTREZ:821 UNIPROT:P27824 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 Upon dissociation from CNX, the heavy chain of (MHC) class I binds β2 microglobulin (b2m) and is incorporated into the peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides for MHCII presentation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CANX"/> <clone/> <bbox w="80.0" h="40.0" x="5090.0" y="2670.0"/> </glyph> <glyph class="macromolecule" id="s532_sa225" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD40 molecule HUGO:CD40 hgnc_id:HGNC:11919 HGNC:11919 ENTREZ:958 UNIPROT:P25942 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:11964292, PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:8760829 Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD40"/> <bbox w="80.0" h="40.0" x="5005.0" y="3310.0"/> <glyph class="unit of information" id="_2fdd945d-18d7-4e7f-9a10-7305d952a688"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5022.5" y="3305.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s533_sa224" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD80 molecule HUGO:CD80 hgnc_id:HGNC:1700 HGNC:1700 ENTREZ:941 UNIPROT:P33681 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:25582338 The expression levels of CD80 and CD83, the molecules involved in T-cell activation, was similar between the two DC subsets (IL4 and IL15) PMID:11964292, PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:22437870 CD80 and CD86 act lic coactivators of T-cells when they interact with CD28 and inhibit T-cells via interactions with CTLA4 PMID:25215878 FLT3 ligand upregulates surface expression of CD80 in DCs. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD80"/> <bbox w="80.0" h="40.0" x="4745.0" y="3330.0"/> <glyph class="unit of information" id="_53d23c38-9471-41d8-af40-d015dbee71ca"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4762.5" y="3325.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1928_sa379" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD36 molecule HUGO:CD36 hgnc_id:HGNC:1663 HGNC:1663 ENTREZ:948 UNIPROT:P16671 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. Cross-present Antigens to Cytotoxic T Lymphocytes. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD36"/> <bbox w="80.0" h="50.0" x="3295.0" y="3475.0"/> <glyph class="unit of information" id="_49444761-f0e6-4289-ab48-3dce9896cc0b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3312.5" y="3470.0"/> </glyph> </glyph> <glyph class="complex" id="s1931_csa78" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ITGAV:ITGB3 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. and cross-present Antigens to Cytotoxic T Lymphocytes The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1931"/> <bbox w="100.0" h="130.0" x="3035.0" y="3475.0"/> <glyph class="macromolecule" id="s1929_sa380"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit alpha V HUGO:ITGAV hgnc_id:HGNC:6150 HGNC:6150 ENTREZ:3685 UNIPROT:P06756 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGAV"/> <bbox w="80.0" h="50.0" x="3045.0" y="3480.0"/> <glyph class="unit of information" id="_6dfeb624-03ff-41e7-9063-f113f4707e02"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3062.5" y="3475.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1930_sa381"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit beta 3 HUGO:ITGB3 hgnc_id:HGNC:6156 HGNC:6156 ENTREZ:3690 UNIPROT:P05106 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGB3"/> <bbox w="80.0" h="50.0" x="3045.0" y="3530.0"/> <glyph class="unit of information" id="_bd6449d2-dcb9-44dc-80f9-aed877cbbf5e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3062.5" y="3525.0"/> </glyph> </glyph> </glyph> <glyph class="simple chemical" id="s1276_sa382" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:16204312 Calcium influx is an early event during perforin-mediated cytotoxicity. PMID:12740575, PMID:15972651 NKG2D signaling inducese PLCG2 phosphorylation and Ca2+ release. The calcium signal generated by PLCG is required for NKG2D-initiated killing. Calcium influx is an early event during perforin-mediated cytotoxicity. PLC-γ2 is absolutely required to regulate degranulation of cytotoxic perforin granules. PMID:22683124 PLCG2-deficient NK cells displayed a partial reduction of conjugate formationwith target tumor cells probably via regulation of Ca2+ fluxes, because a chelator of intracellular Ca2+ also provokes a partial reduction of conjugate formation. PMID:11265639 Cross-linking of NKp80 induces Ca 2+ mobilization and triggering of cytotoxicity in both resting and activated NK cells. PMID:2536067, PMID:1281218 Ligation of Fc gamma RIII alpha (CD16) induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells and stimulates expression of many cytokines via Ca('2+) -depend mechanism. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Ca2+"/> <bbox w="25.0" h="25.0" x="3562.5" y="3107.5"/> </glyph> <glyph class="complex" id="s1934_csa79" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ITGAV:ITGB5 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. Cross-present Antigens to Cytotoxic T Lymphocytes. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1934"/> <bbox w="100.0" h="120.0" x="3395.0" y="3560.0"/> <glyph class="macromolecule" id="s2201_sa383"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit beta 5 HUGO:ITGB5 hgnc_id:HGNC:6160 HGNC:6160 ENTREZ:3693 UNIPROT:P18084 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGB5"/> <bbox w="80.0" h="50.0" x="3405.0" y="3607.5"/> <glyph class="unit of information" id="_3910bb27-ec99-43f5-873e-e19474ac3a84"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3422.5" y="3602.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2202_sa384"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit alpha V HUGO:ITGAV hgnc_id:HGNC:6150 HGNC:6150 ENTREZ:3685 UNIPROT:P06756 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGAV"/> <bbox w="80.0" h="50.0" x="3405.0" y="3565.0"/> <glyph class="unit of information" id="_5e36ddb3-6938-4e49-8159-ee6fe3bffdce"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3422.5" y="3560.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s1935_sa385" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: proteasome subunit alpha 1 HUGO:PSMA1 hgnc_id:HGNC:9530 HGNC:9530 ENTREZ:5682 UNIPROT:P25786 proteasome subunit alpha 2 HUGO:PSMA2 hgnc_id:HGNC:9531 HGNC:9531 ENTREZ:5683 UNIPROT:P25787 proteasome subunit alpha 3 HUGO:PSMA3 hgnc_id:HGNC:9532 HGNC:9532 ENTREZ:5684 UNIPROT:P25788 proteasome subunit alpha 4 HUGO:PSMA4 hgnc_id:HGNC:9533 HGNC:9533 ENTREZ:5685 UNIPROT:P25789 proteasome subunit alpha 5 HUGO:PSMA5 hgnc_id:HGNC:9534 HGNC:9534 ENTREZ:5686 UNIPROT:P28066 proteasome subunit alpha 6 HUGO:PSMA6 hgnc_id:HGNC:9535 HGNC:9535 ENTREZ:5687 UNIPROT:P60900 proteasome subunit alpha 7 HUGO:PSMA7 hgnc_id:HGNC:9536 HGNC:9536 ENTREZ:5688 UNIPROT:O14818 proteasome subunit alpha 8 HUGO:PSMA8 hgnc_id:HGNC:22985 HGNC:22985 ENTREZ:143471 UNIPROT:Q8TAA3 proteasome subunit beta 1 HUGO:PSMB1 hgnc_id:HGNC:9537 HGNC:9537 ENTREZ:5689 UNIPROT:P20618 proteasome subunit beta 2 HUGO:PSMB2 hgnc_id:HGNC:9539 HGNC:9539 ENTREZ:5690 UNIPROT:P49721 proteasome subunit beta 3 HUGO:PSMB3 hgnc_id:HGNC:9540 HGNC:9540 ENTREZ:5691 UNIPROT:P49720 proteasome subunit beta 4 HUGO:PSMB4 hgnc_id:HGNC:9541 HGNC:9541 ENTREZ:5692 UNIPROT:P28070 proteasome subunit beta 5 HUGO:PSMB5 hgnc_id:HGNC:9542 HGNC:9542 ENTREZ:5693 UNIPROT:P28074 proteasome subunit beta 6 HUGO:PSMB6 hgnc_id:HGNC:9543 HGNC:9543 ENTREZ:5694 UNIPROT:P28072 proteasome subunit beta 7 HUGO:PSMB7 hgnc_id:HGNC:9544 HGNC:9544 ENTREZ:5695 UNIPROT:Q99436 proteasome subunit beta 8 HUGO:PSMB8 hgnc_id:HGNC:9545 HGNC:9545 ENTREZ:5696 UNIPROT:P28062 proteasome subunit beta 9 HUGO:PSMB9 hgnc_id:HGNC:9546 HGNC:9546 ENTREZ:5698 UNIPROT:P28065 proteasome subunit beta 10 HUGO:PSMB10 hgnc_id:HGNC:9538 HGNC:9538 ENTREZ:5699 UNIPROT:P40306 proteasome 26S subunit, ATPase 1 HUGO:PSMC1 hgnc_id:HGNC:9547 HGNC:9547 ENTREZ:5700 UNIPROT:P62191 proteasome 26S subunit, ATPase 2 HUGO:PSMC2 hgnc_id:HGNC:9548 HGNC:9548 ENTREZ:5701 UNIPROT:P35998 proteasome 26S subunit, ATPase 3 HUGO:PSMC3 hgnc_id:HGNC:9549 HGNC:9549 ENTREZ:5702 UNIPROT:P17980 proteasome 26S subunit, ATPase 4 HUGO:PSMC4 hgnc_id:HGNC:9551 HGNC:9551 ENTREZ:5704 UNIPROT:P43686 proteasome 26S subunit, ATPase 5 HUGO:PSMC5 hgnc_id:HGNC:9552 HGNC:9552 ENTREZ:5705 UNIPROT:P62195 proteasome 26S subunit, ATPase 6 HUGO:PSMC6 hgnc_id:HGNC:9553 HGNC:9553 ENTREZ:5706 UNIPROT:P62333 proteasome 26S subunit, non-ATPase 1 HUGO:PSMD1 hgnc_id:HGNC:9554 HGNC:9554 ENTREZ:5707 UNIPROT:Q99460 proteasome 26S subunit, non-ATPase 2 HUGO:PSMD2 hgnc_id:HGNC:9559 HGNC:9559 ENTREZ:5708 UNIPROT:Q13200 proteasome 26S subunit, non-ATPase 3 HUGO:PSMD3 hgnc_id:HGNC:9560 HGNC:9560 ENTREZ:5709 UNIPROT:O43242 proteasome 26S subunit, non-ATPase 4 HUGO:PSMD4 hgnc_id:HGNC:9561 HGNC:9561 ENTREZ:5710 UNIPROT:P55036 proteasome 26S subunit, non-ATPase 5 HUGO:PSMD5 hgnc_id:HGNC:9563 HGNC:9563 ENTREZ:5711 UNIPROT:Q16401 proteasome 26S subunit, non-ATPase 6 HUGO:PSMD6 hgnc_id:HGNC:9564 HGNC:9564 ENTREZ:9861 UNIPROT:Q15008 proteasome 26S subunit, non-ATPase 7 HUGO:PSMD7 hgnc_id:HGNC:9565 HGNC:9565 ENTREZ:5713 UNIPROT:P51665 proteasome 26S subunit, non-ATPase 8 HUGO:PSMD8 hgnc_id:HGNC:9566 HGNC:9566 ENTREZ:5714 UNIPROT:P48556 proteasome 26S subunit, non-ATPase 9 HUGO:PSMD9 hgnc_id:HGNC:9567 HGNC:9567 ENTREZ:5715 UNIPROT:O00233 proteasome 26S subunit, non-ATPase 10 HUGO:PSMD10 hgnc_id:HGNC:9555 HGNC:9555 ENTREZ:5716 UNIPROT:O75832 proteasome 26S subunit, non-ATPase 11 HUGO:PSMD11 hgnc_id:HGNC:9556 HGNC:9556 ENTREZ:5717 UNIPROT:O00231 proteasome 26S subunit, non-ATPase 12 HUGO:PSMD12 hgnc_id:HGNC:9557 HGNC:9557 ENTREZ:5718 UNIPROT:O00232 proteasome 26S subunit, non-ATPase 13 HUGO:PSMD13 hgnc_id:HGNC:9558 HGNC:9558 ENTREZ:5719 UNIPROT:Q9UNM6 proteasome 26S subunit, non-ATPase 14 HUGO:PSMD14 hgnc_id:HGNC:16889 HGNC:16889 ENTREZ:10213 UNIPROT:O00487 proteasome activator subunit 1 HUGO:PSME1 hgnc_id:HGNC:9568 HGNC:9568 ENTREZ:5720 UNIPROT:Q06323 proteasome activator subunit 2 HUGO:PSME2 hgnc_id:HGNC:9569 HGNC:9569 ENTREZ:5721 UNIPROT:Q9UL46 proteasome activator subunit 3 HUGO:PSME3 hgnc_id:HGNC:9570 HGNC:9570 ENTREZ:10197 UNIPROT:P61289 proteasome activator subunit 4 HUGO:PSME4 hgnc_id:HGNC:20635 HGNC:20635 ENTREZ:23198 UNIPROT:Q14997 proteasome inhibitor subunit 1 HUGO:PSMF1 hgnc_id:HGNC:9571 HGNC:9571 ENTREZ:9491 UNIPROT:Q92530 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:11717192 The IFN-gamma-responsive immunoproteasome subunits LMP2, LMP7 and MECL1 are up-regulated in immature DC, whereas the other components of the MHC class I presentation machinery, such as PA28, TAP, tapasin, and HLA heavy and light chains, were found to be more abundant in mature DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="proteasome*"/> <bbox w="80.0" h="40.0" x="3415.0" y="2250.0"/> </glyph> <glyph class="macromolecule" id="s634_sa26"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: high mobility group box 1 HUGO:HMGB1 hgnc_id:HGNC:4983 HGNC:4983 ENTREZ:3146 UNIPROT:P09429 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15802534 NK cells induce maturation or killing of immature autologous DCs: prevention of DC lysis by HMGB1 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro IL18 PMID:19571604 HMGB1 produced by colon cancer cells suppressed nodal dendritic cells to disturb host anti-cancer immunity. PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and engages Toll-like receptor4 (TLR4) on dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="HMGB1"/> <bbox w="80.0" h="40.0" x="5835.0" y="450.0"/> </glyph> <glyph class="nucleic acid feature" id="s1936_sa386" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 18 HUGO:IL18 hgnc_id:HGNC:5986 HGNC:5986 ENTREZ:3606 UNIPROT:Q14116 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:9469432 IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells PMID:10679398 The role of IL-18 in innate immunity. PMID:15802534 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro-IL18 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18"/> <bbox w="70.0" h="25.0" x="5430.0" y="1387.5"/> </glyph> <glyph class="nucleic acid feature" id="s1937_sa387" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 18 HUGO:IL18 hgnc_id:HGNC:5986 HGNC:5986 ENTREZ:3606 UNIPROT:Q14116 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:9469432 IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells PMID:10679398 The role of IL-18 in innate immunity. PMID:15802534 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro-IL18 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18"/> <bbox w="90.0" h="25.0" x="5420.0" y="1447.5"/> <glyph class="unit of information" id="_ff8167f5-3f87-49d1-be58-f6208d7643d3"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5455.0" y="1442.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1190_sa388" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 18 HUGO:IL18 hgnc_id:HGNC:5986 HGNC:5986 ENTREZ:3606 UNIPROT:Q14116 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:9469432 IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells PMID:10679398 The role of IL-18 in innate immunity. PMID:15802534 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro-IL18 PMID:14504095, PMID:14662834 IL-18 induces chemotaxis of pDC. PMID:14662834 IL-18 had a direct migratory effect on MoDC as indicated by induction of filamentous actin polymerization and migration in Boyden chamber experiments (MoDC migrated toward an IL-18 gradient in Boyden chamber assays). In epidermal DC, IL-18 was also able to induce filamentous actin polymerization. Therefore,IL-18 might represent a novel mechanism to recruit DC to areas of inflammation. IL-18 up-regulated most strikingly the surface expression of CD54 (ICAM1) and induces F-actin polymerization PMID:11592085 ICAM-1 regulates the migration of dendritic cells into regional lymph nodes References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18"/> <bbox w="80.0" h="40.0" x="5425.0" y="1520.0"/> </glyph> <glyph class="nucleic acid feature" id="s76_sa392" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 beta HUGO:IL1B hgnc_id:HGNC:5992 HGNC:5992 ENTREZ:3553 UNIPROT:P01584 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15802534 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro-IL18 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL1B"/> <bbox w="70.0" h="25.0" x="5550.0" y="1387.5"/> </glyph> <glyph class="nucleic acid feature" id="s78_sa393" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 beta HUGO:IL1B hgnc_id:HGNC:5992 HGNC:5992 ENTREZ:3553 UNIPROT:P01584 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15802534 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro-IL18 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL1B"/> <bbox w="90.0" h="25.0" x="5540.0" y="1457.5"/> <glyph class="unit of information" id="_ec35016f-d99e-40b7-8a97-a18665dbf1bb"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5575.0" y="1452.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1939_sa389" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 beta HUGO:IL1B hgnc_id:HGNC:5992 HGNC:5992 ENTREZ:3553 UNIPROT:P01584 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL1B"/> <bbox w="80.0" h="40.0" x="5545.0" y="1520.0"/> </glyph> <glyph class="macromolecule" id="s703_sa25" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD14 molecule HUGO:CD14 hgnc_id:HGNC:1628 HGNC:1628 ENTREZ:929 UNIPROT:P08571 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and activates TLR4/MyD88 signaling pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II and MHC I). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD14"/> <bbox w="80.0" h="40.0" x="5565.0" y="840.0"/> </glyph> <glyph class="macromolecule" id="s1945_sa394" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine receptor 7 HUGO:CCR7 hgnc_id:HGNC:1608 HGNC:1608 ENTREZ:1236 UNIPROT:P32248 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCR7"/> <bbox w="80.0" h="50.0" x="2765.0" y="615.0"/> <glyph class="unit of information" id="_edaa208a-614f-4c67-a008-939812150dbb"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2782.5" y="610.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1946_sa395" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X-C motif chemokine receptor 4 HUGO:CXCR4 hgnc_id:HGNC:2561 HGNC:2561 ENTREZ:7852 UNIPROT:P61073 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCR4"/> <bbox w="80.0" h="50.0" x="2985.0" y="595.0"/> <glyph class="unit of information" id="_2f65f01e-cde7-4f2a-b5f3-a8f2e675349c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3002.5" y="590.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1947_sa397" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine receptor 7 HUGO:CCR7 hgnc_id:HGNC:1608 HGNC:1608 ENTREZ:1236 UNIPROT:P32248 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCR7"/> <bbox w="80.0" h="50.0" x="2795.0" y="855.0"/> <glyph class="unit of information" id="_7a5ba742-d457-4f77-be77-5541cb84cabd"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2812.5" y="850.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1948_sa398" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X-C motif chemokine receptor 4 HUGO:CXCR4 hgnc_id:HGNC:2561 HGNC:2561 ENTREZ:7852 UNIPROT:P61073 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCR4"/> <bbox w="80.0" h="50.0" x="2985.0" y="775.0"/> <glyph class="unit of information" id="_90ea5f4f-c958-42a9-ae01-f54f05b7979e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3002.5" y="770.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1950_sa400"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 19 HUGO:CCL19 hgnc_id:HGNC:10617 HGNC:10617 ENTREZ:6363 UNIPROT:Q99731 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL19"/> <bbox w="80.0" h="40.0" x="2665.0" y="260.0"/> </glyph> <glyph class="complex" id="s1951_csa80" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CCL19:CCR7 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:11698286 IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1951"/> <bbox w="100.0" h="120.0" x="2805.0" y="380.0"/> <glyph class="macromolecule" id="s1952_sa401"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: C-C motif chemokine receptor 7 HUGO:CCR7 hgnc_id:HGNC:1608 HGNC:1608 ENTREZ:1236 UNIPROT:P32248 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCR7"/> <bbox w="80.0" h="50.0" x="2815.0" y="435.0"/> <glyph class="unit of information" id="_18e0f8b9-6161-4b47-936f-16c1e3d5a62d"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2832.5" y="430.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1953_sa403"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: C-C motif chemokine ligand 19 HUGO:CCL19 hgnc_id:HGNC:10617 HGNC:10617 ENTREZ:6363 UNIPROT:Q99731 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL19"/> <bbox w="80.0" h="40.0" x="2815.0" y="390.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1954_sa404"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X-C motif chemokine ligand 12 HUGO:CXCL12 hgnc_id:HGNC:10672 HGNC:10672 ENTREZ:6387 UNIPROT:P48061 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCL12"/> <bbox w="80.0" h="40.0" x="3025.0" y="200.0"/> </glyph> <glyph class="complex" id="s1955_csa81" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CXCL12:CXCR4 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1955"/> <bbox w="100.0" h="120.0" x="2935.0" y="380.0"/> <glyph class="macromolecule" id="s1956_sa405"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: C-X-C motif chemokine ligand 12 HUGO:CXCL12 hgnc_id:HGNC:10672 HGNC:10672 ENTREZ:6387 UNIPROT:P48061 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCL12"/> <bbox w="80.0" h="40.0" x="2945.0" y="390.0"/> </glyph> <glyph class="macromolecule" id="s1957_sa406"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: C-X-C motif chemokine receptor 4 HUGO:CXCR4 hgnc_id:HGNC:2561 HGNC:2561 ENTREZ:7852 UNIPROT:P61073 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCR4"/> <bbox w="80.0" h="50.0" x="2945.0" y="435.0"/> <glyph class="unit of information" id="_d73d7da6-8e9d-4895-9552-8fa89ffcf7c8"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2962.5" y="430.0"/> </glyph> </glyph> </glyph> <glyph class="phenotype" id="s585_sa396"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22539295 DCs migrate from the periphery to the draining Limph Nodes via a chemokine gradient after receipt of microbial or danger signals. The chemokine receptors CCR7 and CXCR4 are crucial for this process References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Migration"/> <bbox w="220.0" h="35.0" x="2835.0" y="142.5"/> </glyph> <glyph class="complex" id="s660_csa5" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CD14:IRAK2:IRAK4:LY96:MYD88:TIRAP:TLR4 Identifiers_end Maps_Modules_begin: MODEULE:MACROPHAGE MODEULE:MDSC Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. Transfection of dominant negative MyD88 or TIRAP inhibited almost all of the HMGB1- and LPS-induced NF-κB activation. MyD88 recruits members of the death domain-containing serine/threonine IL-1R-associated kinase (IRAK) family. PMID:12620219 PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and activates TLR4/MyD88 signaling pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II and MHC I). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s654"/> <bbox w="203.75" h="220.3125" x="5923.125" y="809.84375"/> <glyph class="macromolecule" id="s676_sa40"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 1 receptor associated kinase 2 HUGO:IRAK2 hgnc_id:HGNC:6113 HGNC:6113 ENTREZ:3656 UNIPROT:O43187 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 MyD88 recruits members of the death domain-containing serine/threonine IL-1R-associated kinase (IRAK) family. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRAK2"/> <bbox w="80.0" h="40.0" x="6016.875" y="959.84375"/> </glyph> <glyph class="macromolecule" id="s678_sa39"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TIR domain containing adaptor protein HUGO:TIRAP hgnc_id:HGNC:17192 HGNC:17192 ENTREZ:114609 UNIPROT:P58753 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TIRAP"/> <bbox w="80.0" h="40.0" x="6016.875" y="919.84375"/> </glyph> <glyph class="macromolecule" id="s679_sa38"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: myeloid differentiation primary response 88 HUGO:MYD88 hgnc_id:HGNC:7562 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. PMID:17704786 DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MYD88"/> <bbox w="80.0" h="40.0" x="5926.875" y="919.84375"/> </glyph> <glyph class="macromolecule" id="s680_sa37"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: lymphocyte antigen 96 HUGO:LY96 hgnc_id:HGNC:17156 HGNC:17156 ENTREZ:23643 UNIPROT:Q9Y6Y9 Identifiers_end Maps_Modules_begin: MODEULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and activates TLR4/MyD88 signaling pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II and MHC I). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LY96"/> <bbox w="80.0" h="40.0" x="5926.875" y="819.84375"/> </glyph> <glyph class="macromolecule" id="s681_sa36"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: toll like receptor 4 HUGO:TLR4 hgnc_id:HGNC:11850 HGNC:11850 ENTREZ:7099 UNIPROT:O00206 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. PMID:16489357, PMID:17704786, PMID:23811849 TLR4 signaling induces antigens for presentation, by DC in tumors. syngeneic WT, Trif-/-, Tlr1-/-, Tlr2-/-, Tlr3-/-, Tlr5-/-, Tlr6-/-, Tlr7-/- or Tlr9-/- DCs could present antigen from dying tumor cells, Tlr4-/- and Myd88-/- DCs were defective in this function PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. PMID:11477091,PMID:14607893 Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10, which is also associated to Th1 responses. In contrast, TLR2 stimulation failed to induce IL-12 p70 and interferon-gamma inducible protein (IP)-10 but resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development. TLR2 stimulation also resulted in preferential induction of IL-8 and p19/IL-23. Thus, Escherichia coli LPS and flagellin, which trigger TLR4 and TLR5, respectively, instruct DCs to stimulate Th1 responses via IL-12p70 production, which depends on the phosphorylation of p38 and c-Jun N-terminal kinase 1/2. In contrast, the TLR2 agonist, Pam3cys, and the Th2 stimulus, schistosome egg Ags: 1) barely induce IL-12p70; 2) stimulate sustained duration and magnitude of extracellular signal-regulated kinase 1/2 phosphorylation, which results in stabilization of the transcription factor c-Fos, a suppressor of IL-12; and 3) yield a Th2 bias. Thus, distinct TLR agonists differentially modulate extracellular signal-regulated kinase signaling, c-Fos activity, and cytokine responses in DCs to stimulate different Th responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TLR4"/> <bbox w="80.0" h="50.0" x="6016.875" y="864.84375"/> <glyph class="unit of information" id="_b90ef8c6-45f2-4c1b-924a-a13ddd62e29f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6034.375" y="859.84375"/> </glyph> </glyph> <glyph class="macromolecule" id="s682_sa35"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 1 receptor associated kinase 4 HUGO:IRAK4 hgnc_id:HGNC:17967 HGNC:17967 ENTREZ:51135 UNIPROT:Q9NWZ3 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12620219 MyD88 mediates a close interaction of the two related IRAK molecules, which is essential to allow IRAK-4 to phosphorylate IRAK-1. Phosphorylation of IRAK-1 reduces its affinity for MyD88, while increasing its affinity for TRAF6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRAK4"/> <bbox w="80.0" h="40.0" x="5926.875" y="969.84375"/> </glyph> <glyph class="macromolecule" id="s707_sa34"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD14 molecule HUGO:CD14 hgnc_id:HGNC:1628 HGNC:1628 ENTREZ:929 UNIPROT:P08571 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849, PMID:16489357, PMID:17704786 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and activates TLR4/MyD88 signaling pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells, probably (MHC II and MHC I). The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD14"/> <bbox w="80.0" h="40.0" x="5926.875" y="869.84375"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s1962_sa421" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 HUGO:IL15 hgnc_id:HGNC:5977 HGNC:5977 ENTREZ:3600 UNIPROT:P40933 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11466332, PMID:14607946 I IFN induces IL-15 and IL-15Rα in human and murine DCs via common receptor. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15"/> <bbox w="90.0" h="25.0" x="5940.0" y="1627.5"/> <glyph class="unit of information" id="_ce31e43d-a390-4e2e-957c-98d5b9278cf1"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5975.0" y="1622.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s1963_sa422" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 HUGO:IL15 hgnc_id:HGNC:5977 HGNC:5977 ENTREZ:3600 UNIPROT:P40933 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10811870, PMID:11466332, PMID:14607946 I IFN induces IL-15 and IL-15Rα in human and murine DCs via common receptor. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15"/> <bbox w="70.0" h="25.0" x="5950.0" y="1567.5"/> </glyph> <glyph class="macromolecule" id="s1964_sa53" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 receptor subunit alpha HUGO:IL15RA hgnc_id:HGNC:5978 HGNC:5978 ENTREZ:3601 UNIPROT:Q13261 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15RA"/> <clone/> <bbox w="80.0" h="50.0" x="6405.0" y="1675.0"/> <glyph class="unit of information" id="_3f1e231b-6730-4d8b-ba13-6f78a7ef12f4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6422.5" y="1670.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1964_sa423" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 receptor subunit alpha HUGO:IL15RA hgnc_id:HGNC:5978 HGNC:5978 ENTREZ:3601 UNIPROT:Q13261 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15RA"/> <clone/> <bbox w="80.0" h="50.0" x="6095.0" y="1685.0"/> <glyph class="unit of information" id="_9b9a9fe6-01cd-4420-9162-cad53ce99405"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6112.5" y="1680.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s1965_sa424" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 receptor subunit alpha HUGO:IL15RA hgnc_id:HGNC:5978 HGNC:5978 ENTREZ:3601 UNIPROT:Q13261 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11466332, PMID:14607946 I IFN induces IL-15 and IL-15Rα in human and murine DCs via common receptor. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15RA"/> <bbox w="70.0" h="25.0" x="6100.0" y="1567.5"/> </glyph> <glyph class="nucleic acid feature" id="s1966_sa425" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 receptor subunit alpha HUGO:IL15RA hgnc_id:HGNC:5978 HGNC:5978 ENTREZ:3601 UNIPROT:Q13261 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11466332, PMID:14607946 I IFN induces IL-15 and IL-15Rα in human and murine DCs via common receptor. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15RA"/> <bbox w="90.0" h="25.0" x="6090.0" y="1627.5"/> <glyph class="unit of information" id="_5a4414f2-df8b-4035-bce0-b6d3a414c42e"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="6125.0" y="1622.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1968_sa426" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 10 HUGO:IL10 hgnc_id:HGNC:5962 HGNC:5962 ENTREZ:3586 UNIPROT:P22301 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming.PMID:18492954 mTOR regulates IL-12 expression through an autocrine action of IL-10 in DC via STAT3. PMID:15573129 DCs derived from transgenic mice that overexpress IL-10 markedly suppressed allogeneic T-cell responses, CTL responses and IL-12 production70. IL-10 might convert iDCs into tolerogenic APCs through decreased expression of co-stimulatory molecules PMID:11254683, PMID:9366401 Mature DCs become resistant to the effects of exogenous IL-10, addition of anti-IL-10 mAb to already matured DCs had no influence on cytokine release and surface phenotype. Mature DCs show enhanced accumulation of IL-10R1 mRNA and intracellular IL-10R protein but reduced membrane IL-10R and IL-10 binding activity. IL10 signaling activates STAT3 in DC PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) PMID:25446896 Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10"/> <bbox w="80.0" h="40.0" x="1415.0" y="1401.25"/> </glyph> <glyph class="nucleic acid feature" id="s1969_sa427" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 10 HUGO:IL10 hgnc_id:HGNC:5962 HGNC:5962 ENTREZ:3586 UNIPROT:P22301 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21191065 Cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. LGALS1 upregulates ID3 expression, then ID3 upregulates expression of IL10 in DC. PMID:17114424 IL-10 production is induced by TLR ligands via MyD88-dependent and TRIF-dependent TLR signals in macrophages and myeloid DC CD40 ligation of macrophages, myeloid DC, and splenic DC populations induces IL-10, whereas no IL-10 production is induced in plasmacytoid DC. 25215878 FLT3L partially antagonized IL-10-mediated inhibition on DCs function (probably via STAT3) and downregulates IL10 mRNA expression in DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10"/> <bbox w="70.0" h="25.0" x="1430.0" y="1567.5"/> </glyph> <glyph class="nucleic acid feature" id="s1970_sa428" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 10 HUGO:IL10 hgnc_id:HGNC:5962 HGNC:5962 ENTREZ:3586 UNIPROT:P22301 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:21191065 Cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. LGALS1 upregulates ID3 expression, then ID3 upregulates expression of IL10 in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL10"/> <bbox w="90.0" h="25.0" x="1420.0" y="1477.5"/> <glyph class="unit of information" id="_4e528104-7584-462d-83c2-6fb38782c5f6"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="1455.0" y="1472.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1972_sa430" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: catenin beta 1 HUGO:CTNNB1 hgnc_id:HGNC:2514 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:24023259 β-Catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8+ T cells PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming,β-catenin enhanced IL-10 induction through mTOR pathway. β-Catenin up-regulates level of mTOR in DCs and activates mTOR signaling. PMID:20705860 β-catenin signaling in DCs is required to induce Treg cells and suppress TH1/TH17 responses. β-catenin signaling in intestinal DCs promotes the expression of Raldh and suppresses the expression of proinflammatory cytokines (IL6, IL23a,IL12p40) but induces IL10 production. PMID:15001769, PMID:17936032 GSK3B phosphorylates beta-catenin and inhibits its activity. Beta-catenin signaling prevents production of inflammatory cytokines IL6, IL-1α, IL-6, TNF-α, and IL-12 p40, But upregulates CCR7, both at the mRNA level and on the plasma membrane. CCR7 is a chemokine receptor important for the migration of DCs from the periphery to T cell areas of lymph nodes. DCs matured by CD activation of beta-catenin signaling alone failed to prime CD4 T cells to produce IFN-γ but did generate high levels of IL10 (Fig. 6A) together with other cytokines (not shown) consistent with type I regulatory T cells References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="β-Catenin*"/> <bbox w="80.0" h="40.0" x="2725.0" y="1210.0"/> <glyph class="state variable" id="_472df690-2aaf-4968-bc29-69ef7c5169e3"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="2720.0" y="1225.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1974_sa499" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B hgnc_id:HGNC:4617 HGNC:4617 ENTREZ:2932 UNIPROT:P49841 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. It activates mTOR and inhibits GSK3B; GSK3 inhibits IL10 expression, and induces IL12 expression References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GSK3β*"/> <bbox w="80.0" h="40.0" x="4135.0" y="1648.75"/> <glyph class="state variable" id="_1d074541-7004-41c3-9424-ae2e8117b545"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4130.0" y="1663.75"/> </glyph> </glyph> <glyph class="complex" id="s1975_csa82" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DEPTOR:MLST8:MTOR:PRAS40*:RPTOR Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: 16469695, 26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR 22504639, 20805416 Impaired mTORC1 signal resulted in the suppression of IL-10 production in DC. IL-10 expression was impaired at both protein and mRNA levels in RaptorDC−/− mice. 19143636 The signalling function of mTOR complex 1 is activated by Rheb-GTP. 20805416 mTOR pathway plays divergent roles during activation and differentiation of myeloid DCs (mDCs) and monocyte-derived DCs (moDCs). Inhibition of mTORC1 in mDCs activated with TLR-dependent or -independent stimuli increased proinflammatory cytokines and NF-κB, whereas IL-10 and STAT3 were blocked. Rapamycin regulated the costimulatory/surface molecules CD86, programmed death ligand-1, and CD25 on mDCs and significantly increased the T cell allostimulatory potential of mDCs. In contrast, rapamycin suppressed immunostimulatory molecules and the allostimulatory potential of LPS-stimulated moDCs by an inability to augment NF-κB signaling. In differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively activated by GM-CSF to induce DC differentiation in an mTORC1-dependent manner. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="mTORC1*"/> <clone/> <bbox w="210.0" h="210.0" x="3120.0" y="1015.0"/> <glyph class="macromolecule" id="s1976_sa434"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: mechanistic target of rapamycin HUGO:MTOR hgnc_id:HGNC:3942 HGNC:3942 ENTREZ:2475 UNIPROT:P42345 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming,β-catenin enhanced IL-10 induction through mTOR pathway. β-Catenin up-regulates level of mTOR in DCs and activates mTOR signaling. PMID:18492954 mTOR regulates IL-12 expression through an autocrine action of IL-10 in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MTOR"/> <clone/> <bbox w="80.0" h="40.0" x="3135.0" y="1150.0"/> </glyph> <glyph class="macromolecule" id="s1977_sa435"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: regulatory associated protein of MTOR complex 1 HUGO:RPTOR hgnc_id:HGNC:30287 HGNC:30287 ENTREZ:57521 UNIPROT:Q8N122 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RPTOR"/> <clone/> <bbox w="80.0" h="40.0" x="3135.0" y="1090.0"/> </glyph> <glyph class="macromolecule" id="s1978_sa436"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: MTOR associated protein, LST8 homolog HUGO:MLST8 hgnc_id:HGNC:24825 HGNC:24825 ENTREZ:64223 UNIPROT:Q9BVC4 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MLST8"/> <clone/> <bbox w="80.0" h="40.0" x="3225.0" y="1090.0"/> </glyph> <glyph class="macromolecule" id="s1979_sa437"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: DEP domain containing MTOR interacting protein HUGO:DEPTOR hgnc_id:HGNC:22953 HGNC:22953 ENTREZ:64798 UNIPROT:Q8TB45 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="DEPTOR"/> <clone/> <bbox w="80.0" h="40.0" x="3225.0" y="1140.0"/> </glyph> <glyph class="macromolecule" id="s1980_sa438"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: AKT1 substrate 1 HUGO:AKT1S1 hgnc_id:HGNC:28426 HGNC:28426 ENTREZ:84335 UNIPROT:Q96B36 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PRAS40*"/> <clone/> <bbox w="80.0" h="40.0" x="3225.0" y="1030.0"/> </glyph> </glyph> <glyph class="complex" id="s1975_csa83" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:DEPTOR:MLST8:MTOR:PRAS40*:RPTOR Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: 16469695, 26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR 22504639, 20805416 Impaired mTORC1 signal resulted in the suppression of IL-10 production in DC. IL-10 expression was impaired at both protein and mRNA levels in RaptorDC−/− mice. 19143636 The signalling function of mTOR complex 1 is activated by Rheb-GTP. 20805416 mTOR pathway plays divergent roles during activation and differentiation of myeloid DCs (mDCs) and monocyte-derived DCs (moDCs). Inhibition of mTORC1 in mDCs activated with TLR-dependent or -independent stimuli increased proinflammatory cytokines and NF-κB, whereas IL-10 and STAT3 were blocked. Rapamycin regulated the costimulatory/surface molecules CD86, programmed death ligand-1, and CD25 on mDCs and significantly increased the T cell allostimulatory potential of mDCs. In contrast, rapamycin suppressed immunostimulatory molecules and the allostimulatory potential of LPS-stimulated moDCs by an inability to augment NF-κB signaling. In differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively activated by GM-CSF to induce DC differentiation in an mTORC1-dependent manner. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="mTORC1*"/> <clone/> <bbox w="210.0" h="210.0" x="3480.0" y="1015.0"/> <glyph class="macromolecule" id="s1976_sa439"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: mechanistic target of rapamycin HUGO:MTOR hgnc_id:HGNC:3942 HGNC:3942 ENTREZ:2475 UNIPROT:P42345 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming,β-catenin enhanced IL-10 induction through mTOR pathway. β-Catenin up-regulates level of mTOR in DCs and activates mTOR signaling. PMID:18492954 mTOR regulates IL-12 expression through an autocrine action of IL-10 in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MTOR"/> <clone/> <bbox w="80.0" h="40.0" x="3495.0" y="1150.0"/> </glyph> <glyph class="macromolecule" id="s1977_sa440"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: regulatory associated protein of MTOR complex 1 HUGO:RPTOR hgnc_id:HGNC:30287 HGNC:30287 ENTREZ:57521 UNIPROT:Q8N122 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RPTOR"/> <clone/> <bbox w="80.0" h="40.0" x="3495.0" y="1090.0"/> </glyph> <glyph class="macromolecule" id="s1978_sa441"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: MTOR associated protein, LST8 homolog HUGO:MLST8 hgnc_id:HGNC:24825 HGNC:24825 ENTREZ:64223 UNIPROT:Q9BVC4 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MLST8"/> <clone/> <bbox w="80.0" h="40.0" x="3585.0" y="1090.0"/> </glyph> <glyph class="macromolecule" id="s1979_sa442"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: DEP domain containing MTOR interacting protein HUGO:DEPTOR hgnc_id:HGNC:22953 HGNC:22953 ENTREZ:64798 UNIPROT:Q8TB45 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="DEPTOR"/> <clone/> <bbox w="80.0" h="40.0" x="3585.0" y="1140.0"/> </glyph> <glyph class="macromolecule" id="s1980_sa443"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: AKT1 substrate 1 HUGO:AKT1S1 hgnc_id:HGNC:28426 HGNC:28426 ENTREZ:84335 UNIPROT:Q96B36 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:16469695, PMID:26159692 mTOR Complex 1 (mTORC1) is composed of mTOR itself, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8) and the recently identified PRAS40 and DEPTOR References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PRAS40*"/> <clone/> <bbox w="80.0" h="40.0" x="3585.0" y="1030.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s110_sa444" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12B HUGO:IL12B hgnc_id:HGNC:5970 HGNC:5970 ENTREZ:3593 UNIPROT:P29460 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10, probably via STAT3. GSK3 inhibits IL10 expression, and induces IL12 expression. PMID:10993913 Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. PMID:9174615 IL10 inhibits mRNA expression of p35 and p40 of IL12, probably via STAT3 PMID:25446896 Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. PMID:14504095 CD40L stimulation induces mRNA espression of p40 and p35 subunits of IL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p40*"/> <bbox w="70.0" h="25.0" x="5466.5" y="1711.25"/> </glyph> <glyph class="nucleic acid feature" id="s220_sa445" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12A HUGO:IL12A hgnc_id:HGNC:5969 HGNC:5969 ENTREZ:3592 UNIPROT:P29459 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p35*"/> <bbox w="90.0" h="25.0" x="5560.0" y="1807.5"/> <glyph class="unit of information" id="_35aa9254-bcee-4be4-afc1-97f1fa94441e"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5595.0" y="1802.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s219_sa446" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12A HUGO:IL12A hgnc_id:HGNC:5969 HGNC:5969 ENTREZ:3592 UNIPROT:P29459 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10, probably via STAT3. GSK3 inhibits IL10 expression, and induces IL12 expression PMID:10993913 Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. PMID:9174615 IL10 inhibits mRNA expression of p35 and p40 of IL12, probably via STAT3 PMID:25446896 Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. PMID:14504095 CD40L stimulation induces mRNA espression of p40 and p35 subunits of IL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p35*"/> <bbox w="70.0" h="25.0" x="5560.0" y="1711.25"/> </glyph> <glyph class="nucleic acid feature" id="s114_sa447" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12B HUGO:IL12B hgnc_id:HGNC:5970 HGNC:5970 ENTREZ:3593 UNIPROT:P29460 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p40*"/> <bbox w="90.0" h="25.0" x="5450.0" y="1807.5"/> <glyph class="unit of information" id="_9d6a948c-1825-471d-91e0-c0b64566d0c7"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5485.0" y="1802.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s221_sa448" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12A HUGO:IL12A hgnc_id:HGNC:5969 HGNC:5969 ENTREZ:3592 UNIPROT:P29459 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p35*"/> <bbox w="80.0" h="40.0" x="5555.0" y="1888.75"/> </glyph> <glyph class="macromolecule" id="s117_sa449" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12B HUGO:IL12B hgnc_id:HGNC:5970 HGNC:5970 ENTREZ:3593 UNIPROT:P29460 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p40*"/> <bbox w="80.0" h="40.0" x="5461.5" y="1888.75"/> </glyph> <glyph class="simple chemical" id="s745_sa480" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:12040186 The activated PI3K converts the plasma membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3]. PMID:9438848 PI3K product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav proteins PMID:12393695 SHIP1 inhinits NK cells activation via bloking of PI3K pathway. It hydrolyzes the 5′-phosphate of PI3,4,5P3l eading to its conversion to PI3,4P2. PMID:20363967, PMID:16204085 Src homology 2-containing inositol 5'-phosphatase 1 negatively regulates IFN-gamma production by natural killer cells stimulated with antibody-coated tumor cells and interleukin-12, probably via inhibition of PI3K pathway and downstream ERK signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PIP3*"/> <bbox w="70.0" h="25.0" x="3675.0" y="1616.25"/> </glyph> <glyph class="macromolecule" id="s1114_sa481" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: 3-phosphoinositide dependent protein kinase 1 HUGO:PDPK1 hgnc_id:HGNC:8816 HGNC:8816 ENTREZ:5170 UNIPROT:O15530 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11687500 Binding to second messenger lipids allows PDK1 and AKT (PKB) to interact with each other, resulting in the phosphorylation and consequent activation of AKT (PKB). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PDPK1"/> <bbox w="80.0" h="40.0" x="3880.0" y="1588.75"/> </glyph> <glyph class="macromolecule" id="s1113_sa482" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: AKT serine/threonine kinase 1 HUGO:AKT1 hgnc_id:HGNC:391 HGNC:391 ENTREZ:207 UNIPROT:P31749 AKT serine/threonine kinase 2 HUGO:AKT2 hgnc_id:HGNC:392 HGNC:392 ENTREZ:208 UNIPROT:P31751 AKT serine/threonine kinase 3 HUGO:AKT3 hgnc_id:HGNC:393 HGNC:393 ENTREZ:10000 UNIPROT:Q9Y243 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:11687500 Binding to second messenger lipids allows PDK1 and AKT (PKB) to interact with each other, resulting in the phosphorylation and consequent activation of AKT (PKB). PMID:18492954 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. PMID:11387313, PMID:9553146 Probably PI3K inhibits p38 via AKT References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="AKT*"/> <bbox w="80.0" h="40.0" x="3915.0" y="1378.75"/> <glyph class="state variable" id="_306a5d88-5649-4a10-84f1-c0a48d3dd32d"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3910.0" y="1393.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s1118_sa483" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: AKT serine/threonine kinase 1 HUGO:AKT1 hgnc_id:HGNC:391 HGNC:391 ENTREZ:207 UNIPROT:P31749 AKT serine/threonine kinase 2 HUGO:AKT2 hgnc_id:HGNC:392 HGNC:392 ENTREZ:208 UNIPROT:P31751 AKT serine/threonine kinase 3 HUGO:AKT3 hgnc_id:HGNC:393 HGNC:393 ENTREZ:10000 UNIPROT:Q9Y243 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:11687500 Binding to second messenger lipids allows PDK1 and AKT (PKB) to interact with each other, resulting in the phosphorylation and consequent activation of AKT (PKB). PMID:18492954 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. PMID:11387313, PMID:9553146 Probably PI3K inhibits p38 via AKT References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="AKT*"/> <bbox w="80.0" h="40.0" x="3915.0" y="1308.75"/> <glyph class="state variable" id="_8602d6e2-750e-4884-a0d2-cfb7756d492a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="3907.5" y="1323.75"/> </glyph> </glyph> <glyph class="complex" id="s1115_csa89" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:PDPK1:PIP3* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1115"/> <bbox w="100.0" h="120.0" x="3775.0" y="1378.75"/> <glyph class="macromolecule" id="s1116_sa488"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: 3-phosphoinositide dependent protein kinase 1 HUGO:PDPK1 hgnc_id:HGNC:8816 HGNC:8816 ENTREZ:5170 UNIPROT:O15530 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11687500 Binding to second messenger lipids allows PDK1 and AKT (PKB) to interact with each other, resulting in the phosphorylation and consequent activation of AKT (PKB). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PDPK1"/> <bbox w="80.0" h="40.0" x="3785.0" y="1388.75"/> </glyph> <glyph class="simple chemical" id="s1117_sa489"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> MODULE:DC PMID:12040186 The activated PI3K converts the plasma membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3]. PMID:9438848 PI3K product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav proteins </body> </html> </notes> <label text="PIP3*"/> <bbox w="70.0" h="25.0" x="3790.0" y="1446.25"/> </glyph> </glyph> <glyph class="complex" id="s1172_csa90" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TSC1:TSC2 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:12906785, PMID:19022819 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TSC1:TSC2"/> <bbox w="100.0" h="140.0" x="3775.0" y="1010.0"/> <glyph class="macromolecule" id="s1173_sa490"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: tuberous sclerosis 1 HUGO:TSC1 hgnc_id:HGNC:12362 HGNC:12362 ENTREZ:7248 UNIPROT:Q92574 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. It activates mTOR and inhibits GSK3B; GSK3 inhibits IL10 expression, and induces IL12 expression PMID:12906785, PMID:19022819 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TSC1"/> <bbox w="80.0" h="40.0" x="3785.0" y="1030.0"/> </glyph> <glyph class="macromolecule" id="s1174_sa491"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: tuberous sclerosis 2 HUGO:TSC2 hgnc_id:HGNC:12363 HGNC:12363 ENTREZ:7249 UNIPROT:P49815 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. It activates mTOR and inhibits GSK3B; GSK3 inhibits IL10 expression, and induces IL12 expression References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TSC2"/> <bbox w="80.0" h="40.0" x="3785.0" y="1070.0"/> <glyph class="state variable" id="_b9439723-6a2b-4c15-be26-7d5152638352"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3780.0" y="1085.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s1185_csa91" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TSC1:TSC2 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:12906785, PMID:19022819 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TSC1:TSC2"/> <bbox w="100.0" h="140.0" x="3775.0" y="1210.0"/> <glyph class="macromolecule" id="s1186_sa492"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: tuberous sclerosis 1 HUGO:TSC1 hgnc_id:HGNC:12362 HGNC:12362 ENTREZ:7248 UNIPROT:Q92574 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. It activates mTOR and inhibits GSK3B; GSK3 inhibits IL10 expression, and induces IL12 expression PMID:12906785, PMID:19022819 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TSC1"/> <bbox w="80.0" h="40.0" x="3785.0" y="1230.0"/> </glyph> <glyph class="macromolecule" id="s1187_sa493"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: tuberous sclerosis 2 HUGO:TSC2 hgnc_id:HGNC:12363 HGNC:12363 ENTREZ:7249 UNIPROT:P49815 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. It activates mTOR and inhibits GSK3B; GSK3 inhibits IL10 expression, and induces IL12 expression References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TSC2"/> <bbox w="80.0" h="40.0" x="3785.0" y="1270.0"/> <glyph class="state variable" id="_24a5f7fd-7231-4a2f-b3eb-fe45dc710803"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="3777.5" y="1285.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s1176_csa92" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GDP:RHEB Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:12906785, PMID:19022819 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1176"/> <bbox w="100.0" h="120.0" x="3555.0" y="1280.0"/> <glyph class="macromolecule" id="s1177_sa494"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Ras homolog enriched in brain HUGO:RHEB hgnc_id:HGNC:10011 HGNC:10011 ENTREZ:6009 UNIPROT:Q15382 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:18492954 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. PMID:19143636 The signalling function of mTOR complex 1 is activated by Rheb-GTP References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RHEB"/> <bbox w="80.0" h="40.0" x="3565.0" y="1300.0"/> </glyph> <glyph class="simple chemical" id="s1179_sa495"> <label text="GDP"/> <bbox w="70.0" h="25.0" x="3570.0" y="1357.5"/> </glyph> </glyph> <glyph class="complex" id="s1178_csa93" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GTP:RHEB Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1178"/> <bbox w="100.0" h="120.0" x="3355.0" y="1280.0"/> <glyph class="macromolecule" id="s1175_sa496"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Ras homolog enriched in brain HUGO:RHEB hgnc_id:HGNC:10011 HGNC:10011 ENTREZ:6009 UNIPROT:Q15382 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:18492954 AKT activates Rapamycin associated protein FRAP2 ( mTOR ) probably through Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. PMID:19143636 The signalling function of mTOR complex 1 is activated by Rheb-GTP References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RHEB"/> <bbox w="80.0" h="40.0" x="3365.0" y="1290.0"/> </glyph> <glyph class="simple chemical" id="s1180_sa497"> <label text="GTP"/> <bbox w="70.0" h="25.0" x="3370.0" y="1347.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1991_sa498" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: phosphatase and tensin homolog HUGO:PTEN hgnc_id:HGNC:9588 HGNC:9588 ENTREZ:5728 UNIPROT:P60484 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 BMDCs lacking PTEN produced lower amounts of IL-12 than control BMDCs on LPS stimulation, indicating that the products of PI3Ks, phosphatidylinositol(3,4,5)trisphosphate in particular, are indeed critical for the regulation of IL-12 expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PTEN"/> <bbox w="80.0" h="40.0" x="3555.0" y="1628.75"/> </glyph> <glyph class="macromolecule" id="s1992_sa433" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: glycogen synthase kinase 3 beta HUGO:GSK3B hgnc_id:HGNC:4617 HGNC:4617 ENTREZ:2932 UNIPROT:P49841 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. It activates mTOR and inhibits GSK3B; GSK3 inhibits IL10 expression, and induces IL12 expression References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GSK3β*"/> <bbox w="80.0" h="40.0" x="4135.0" y="1728.75"/> <glyph class="state variable" id="_0a6476ef-1be3-46d7-92e8-043c965664a1"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4127.5" y="1743.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s1993_sa211" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: SMAD family member 3 HUGO:SMAD3 hgnc_id:HGNC:6769 HGNC:6769 ENTREZ:4088 UNIPROT:P84022 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11792802, PMID:12809600 The canonical TGFB signalling pathway involves phosphorylation of the carboxy-terminal serine residue of the internal modulator SMAD proteins, SMAD2 or SMAD3, by the activated receptors. This phosphorylation induces oligomerization of SMAD2 or SMAD3 with SMAD4, which is necessary for nuclear translocation. PMID:21042762 Inhibition of TGF-ß signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs. Smad2/3 somehow suppresses IRF3 phosphorylation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SMAD3"/> <bbox w="80.0" h="40.0" x="1895.0" y="1200.0"/> <glyph class="state variable" id="_cde29609-0935-4d4d-9ef8-e81fe0abde65"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="1887.5" y="1215.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1994_sa476" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha HUGO:PIK3CA hgnc_id:HGNC:8975 HGNC:8975 ENTREZ:5290 UNIPROT:P42336 DSN1 homolog, MIS12 kinetochore complex component HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta HUGO:PIK3CB hgnc_id:HGNC:8976 HGNC:8976 ENTREZ:5291 UNIPROT:P42338 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta HUGO:PIK3CD hgnc_id:HGNC:8977 HGNC:8977 ENTREZ:5293 UNIPROT:O00329 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma HUGO:PIK3CG hgnc_id:HGNC:8978 HGNC:8978 ENTREZ:5294 UNIPROT:P48736 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: REACTOME:61074 KEGG:5290 ATLASONC:PIK3CAID415ch3q26 WIKI:PIK3CA phosphoinositide-3-kinase, catalytic, beta polypeptide REACTOME:61076 KEGG:5291 ATLASONC:GC_PIK3CB WIKI:PIK3CB phosphoinositide-3-kinase, catalytic, delta polypeptide REACTOME:61078 KEGG:5293 ATLASONC:PIK3CDID46261ch1p36 WIKI:PIK3CD phosphoinositide-3-kinase, catalytic, gamma polypeptide REACTOME:61080 KEGG:5294 ATLASONC:GC_PIK3CG WIKI:PIK3CG PMID:18492954 P3K activates Rapamycin associated protein FRAP2 ( mTOR ) probably through AKT and Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="p110*"/> <clone/> <bbox w="80.0" h="40.0" x="3790.0" y="1748.75"/> </glyph> <glyph class="macromolecule" id="s1994_sa477" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha HUGO:PIK3CA hgnc_id:HGNC:8975 HGNC:8975 ENTREZ:5290 UNIPROT:P42336 DSN1 homolog, MIS12 kinetochore complex component HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta HUGO:PIK3CB hgnc_id:HGNC:8976 HGNC:8976 ENTREZ:5291 UNIPROT:P42338 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta HUGO:PIK3CD hgnc_id:HGNC:8977 HGNC:8977 ENTREZ:5293 UNIPROT:O00329 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma HUGO:PIK3CG hgnc_id:HGNC:8978 HGNC:8978 ENTREZ:5294 UNIPROT:P48736 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: REACTOME:61074 KEGG:5290 ATLASONC:PIK3CAID415ch3q26 WIKI:PIK3CA phosphoinositide-3-kinase, catalytic, beta polypeptide REACTOME:61076 KEGG:5291 ATLASONC:GC_PIK3CB WIKI:PIK3CB phosphoinositide-3-kinase, catalytic, delta polypeptide REACTOME:61078 KEGG:5293 ATLASONC:PIK3CDID46261ch1p36 WIKI:PIK3CD phosphoinositide-3-kinase, catalytic, gamma polypeptide REACTOME:61080 KEGG:5294 ATLASONC:GC_PIK3CG WIKI:PIK3CG PMID:18492954 P3K activates Rapamycin associated protein FRAP2 ( mTOR ) probably through AKT and Tuberin/GTP-binding protein Ras homolog enriched in brain ( RHEB ) pathway. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="p110*"/> <clone/> <bbox w="80.0" h="40.0" x="3790.0" y="1658.75"/> </glyph> <glyph class="macromolecule" id="s1995_sa474" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: phosphoinositide-3-kinase regulatory subunit 1 HUGO:PIK3R1 hgnc_id:HGNC:8979 HGNC:8979 ENTREZ:5295 UNIPROT:P27986 phosphoinositide-3-kinase regulatory subunit 2 HUGO:PIK3R2 hgnc_id:HGNC:8980 HGNC:8980 ENTREZ:5296 UNIPROT:O00459 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:11687500 The class IA PI3Ks, which transmit signals from tyrosine kinase-coupled receptors, are heterodimeric proteins having a p110 catalytic subunit associated with a p85, p55, or p50 regulatory subunit. PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. PMID:12154357 Phosphoinositide 3-kinase (PI3K) negatively regulates IL-12 synthesis by DCs PMID:20805416 In differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively activated by GM-CSF References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PI3KR(p85)*"/> <clone/> <bbox w="80.0" h="40.0" x="3905.0" y="1788.75"/> </glyph> <glyph class="macromolecule" id="s1995_sa475" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: phosphoinositide-3-kinase regulatory subunit 1 HUGO:PIK3R1 hgnc_id:HGNC:8979 HGNC:8979 ENTREZ:5295 UNIPROT:P27986 phosphoinositide-3-kinase regulatory subunit 2 HUGO:PIK3R2 hgnc_id:HGNC:8980 HGNC:8980 ENTREZ:5296 UNIPROT:O00459 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:11687500 The class IA PI3Ks, which transmit signals from tyrosine kinase-coupled receptors, are heterodimeric proteins having a p110 catalytic subunit associated with a p85, p55, or p50 regulatory subunit. PMID:18492954 TLR2/4 signaling induced the phosphorylation of TSC2 and GSK3 in DC via PI3K-AKT pathway. PMID:12154357 Phosphoinositide 3-kinase (PI3K) negatively regulates IL-12 synthesis by DCs PMID:20805416 In differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively activated by GM-CSF References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PI3KR(p85)*"/> <clone/> <bbox w="80.0" h="40.0" x="3900.0" y="1708.75"/> </glyph> <glyph class="macromolecule" id="s2000_sa500" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon alpha 2 HUGO:IFNA2 hgnc_id:HGNC:5423 HGNC:5423 ENTREZ:3440 UNIPROT:P01563 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors. Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines RANTES, MIP-1α, and, especially, MIP-1β . Also IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNA"/> <bbox w="80.0" h="40.0" x="5935.0" y="2150.0"/> </glyph> <glyph class="macromolecule" id="s2001_sa501" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon beta 1 HUGO:IFNB1 hgnc_id:HGNC:5434 HGNC:5434 ENTREZ:3456 UNIPROT:P01574 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:14607946 DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNB"/> <bbox w="80.0" h="40.0" x="6095.0" y="2140.0"/> </glyph> <glyph class="nucleic acid feature" id="s2002_sa502" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon alpha 2 HUGO:IFNA2 hgnc_id:HGNC:5423 HGNC:5423 ENTREZ:3440 UNIPROT:P01563 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors. Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines RANTES, MIP-1α, and, especially, MIP-1β . Also IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNA"/> <bbox w="90.0" h="25.0" x="5920.0" y="2077.5"/> <glyph class="unit of information" id="_0b419884-8abd-44fd-834f-ab0d0536547d"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5955.0" y="2072.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2003_sa503" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon beta 1 HUGO:IFNB1 hgnc_id:HGNC:5434 HGNC:5434 ENTREZ:3456 UNIPROT:P01574 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:14607946 DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNB"/> <bbox w="90.0" h="25.0" x="6090.0" y="2077.5"/> <glyph class="unit of information" id="_4e1823cb-d2bf-44d3-bde1-1a4e431d0e4b"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="6125.0" y="2072.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2004_sa504" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon alpha 2 HUGO:IFNA2 hgnc_id:HGNC:5423 HGNC:5423 ENTREZ:3440 UNIPROT:P01563 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors. Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines RANTES, MIP-1α, and, especially, MIP-1β . Also IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) PMID:15771572, PMID:10364556 Plasmacytoid pre-DCs (pDCs) are the main type I IFN producers in humans and mice References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNA"/> <bbox w="70.0" h="25.0" x="5930.0" y="2007.5"/> </glyph> <glyph class="nucleic acid feature" id="s2005_sa505" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon beta 1 HUGO:IFNB1 hgnc_id:HGNC:5434 HGNC:5434 ENTREZ:3456 UNIPROT:P01574 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:14607946 DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNB"/> <bbox w="70.0" h="25.0" x="6100.0" y="2007.5"/> </glyph> <glyph class="macromolecule" id="s133_sa506" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 11 HUGO:MAPK11 hgnc_id:HGNC:6873 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 DSN1 homolog, MIS12 kinetochore complex component HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410 mitogen-activated protein kinase 12 HUGO:MAPK12 hgnc_id:HGNC:6874 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 mitogen-activated protein kinase 13 HUGO:MAPK13 hgnc_id:HGNC:6875 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 mitogen-activated protein kinase 14 HUGO:MAPK14 hgnc_id:HGNC:6876 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11 REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12 REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13 REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14 PMID:12154357 p38 activity was higher in wortmannin-treated PI3K+/+ BMDCs than in nontreated BMDCs, So PI3K inhibits p38 signaling. Treatment of DCs with SB203580, a specific inhibitor of p38, greatly reduced the production of IL-12p70 by DCs PMID:11387313, PMID:9553146 Probably PI3K inhibits p38 via AKT PMID:11238627 SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-α. PMID:25582338 IL-15 has been shown to induce phosphorylation of STAT3 or p38 MAPK. But increased STAT3 and p38 MAPK activities in IL-15 DCs was associated with LPS/TNFα treatment and was unique to IL-15 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="p38*"/> <bbox w="80.0" h="40.0" x="4395.0" y="1790.0"/> <glyph class="state variable" id="_aa54b917-5cb5-4d26-bfc6-a9b6b6e17547"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4390.0" y="1804.9681"/> </glyph> </glyph> <glyph class="macromolecule" id="s134_sa507" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 11 HUGO:MAPK11 hgnc_id:HGNC:6873 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 DSN1 homolog, MIS12 kinetochore complex component HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410 mitogen-activated protein kinase 12 HUGO:MAPK12 hgnc_id:HGNC:6874 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 mitogen-activated protein kinase 13 HUGO:MAPK13 hgnc_id:HGNC:6875 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 mitogen-activated protein kinase 14 HUGO:MAPK14 hgnc_id:HGNC:6876 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11 REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12 REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13 REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14 PMID:12154357 p38 activity was higher in wortmannin-treated PI3K+/+ BMDCs than in nontreated BMDCs, So PI3K inhibits p38 signaling. Treatment of DCs with SB203580, a specific inhibitor of p38, greatly reduced the production of IL-12p70 by DCs PMID:11387313, PMID:9553146 Probably PI3K inhibits p38 via AKT PMID:11238627 SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-α. PMID:25582338 IL-15 has been shown to induce phosphorylation of STAT3 or p38 MAPK. But increased STAT3 and p38 MAPK activities in IL-15 DCs was associated with LPS/TNFα treatment and was unique to IL-15 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="p38*"/> <bbox w="80.0" h="40.0" x="4395.0" y="1870.0"/> <glyph class="state variable" id="_68685bd9-a9ff-4281-9c17-4bf0dd1f2d4e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4387.5" y="1884.9681"/> </glyph> </glyph> <glyph class="macromolecule" id="s2007_sa509" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD80 molecule HUGO:CD80 hgnc_id:HGNC:1700 HGNC:1700 ENTREZ:941 UNIPROT:P33681 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:25582338 The expression levels of CD80 and CD83, the molecules involved in T-cell activation, was similar between the two DC subsets (IL4 and IL15) PMID:11964292, PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:22437870 CD80 and CD86 act lic coactivators of T-cells when they interact with CD28 and inhibit T-cells via interactions with CTLA4 PMID:25215878 FLT3 ligand upregulates surface expression of CD80 in DCs. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD80"/> <bbox w="80.0" h="40.0" x="4745.0" y="3208.75"/> <glyph class="unit of information" id="_827ab4d4-8953-4849-a3ac-54ecc5b49c09"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4762.5" y="3203.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s2008_sa510" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD86 molecule HUGO:CD86 hgnc_id:HGNC:1705 HGNC:1705 ENTREZ:942 UNIPROT:P42081 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:20805416 Expression of CD86, a critical costimulatory molecule for efficient T cell priming, is enhanced in activated mDCs during mTOR inhibition This phenotype was not observed in moDCs, in which surface expression of CD80 and CD86 was inhibited by rapamycin. PMID:11964292,PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:22437870 CD80 and CD86 act lic coactivators of T-cells when they interact with CD28 and inhibit T-cells via interactions with CTLA4 PMID:10477595, PMID:8920882, PMID: 25215878 FLT3L induces Ag-presenting ability of Dcs. Probably via induction of surface expression of class II MHC and CD86. PMID:22076556, PMID:21220452, PMID:24218453 In immature DCs, internalization of MHC class II molecules from the plasma membrane may require the ubiquitin ligase MARCH1, which is controlled by interleukin-10 (IL-10). CD83 on mature DCs prevents this ubiquitylation of MHC class II molecules and thus stabilizes MHC class II molecules on the cell surface. Addidionally it prevents CD86 ubiquitinqtion. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD86"/> <bbox w="80.0" h="40.0" x="4625.0" y="3208.75"/> <glyph class="state variable" id="_d052acde-8b31-4550-bddb-f607dfb07d8c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4620.0" y="3223.75"/> </glyph> <glyph class="unit of information" id="_d0639e88-f42b-4dbd-9d0f-3a3b8db2c959"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4642.5" y="3203.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s2009_sa511" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD83 molecule HUGO:CD83 hgnc_id:HGNC:1703 HGNC:1703 ENTREZ:9308 UNIPROT:Q01151 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:21220452, PMID:24218453 In immature DCs, internalization of MHC class II molecules from the plasma membrane may require the ubiquitin ligase MARCH1, which is controlled by interleukin-10 (IL-10). CD83 on mature DCs prevents this ubiquitylation of MHC class II molecules and thus stabilizes MHC class II molecules on the cell surface. Addidionally it prevents CD86 ubiquitinqtion. PMID:11238627 SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-α. PMID:25582338 The expression levels of CD80 and CD83, the molecules involved in T-cell activation, was similar between the two DC subsets (IL4 and IL15) PMID:25215878 FLT3 ligand upregulates surface expression of CD83 in DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD83"/> <bbox w="80.0" h="50.0" x="4295.0" y="3205.0"/> <glyph class="unit of information" id="_7d5486b5-8830-459d-be4c-31d368be8eb7"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4312.5" y="3200.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2010_sa512" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD83 molecule HUGO:CD83 hgnc_id:HGNC:1703 HGNC:1703 ENTREZ:9308 UNIPROT:Q01151 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:21220452, PMID:24218453 In immature DCs, internalization of MHC class II molecules from the plasma membrane may require the ubiquitin ligase MARCH1, which is controlled by interleukin-10 (IL-10). CD83 on mature DCs prevents this ubiquitylation of MHC class II molecules and thus stabilizes MHC class II molecules on the cell surface. Addidionally it prevents CD86 ubiquitinqtion. PMID:11238627 SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-α. PMID:25582338 The expression levels of CD80 and CD83, the molecules involved in T-cell activation, was similar between the two DC subsets (IL4 and IL15) PMID:25215878 FLT3 ligand upregulates surface expression of CD83 in DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD83"/> <bbox w="80.0" h="50.0" x="4305.0" y="3365.0"/> <glyph class="unit of information" id="_e943c3df-e8ae-4d6c-bb08-d2caba8e51c5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4322.5" y="3360.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2012_sa514" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:11238627 SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-α. PMID:11306493 IL4 signaling upregulates CD1a on cell surface of DC cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1A"/> <bbox w="80.0" h="50.0" x="5855.0" y="3085.0"/> <glyph class="unit of information" id="_4c2c3390-65ba-4307-bf3b-399a705f8244"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5872.5" y="3080.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2013_sa515" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: integrin subunit alpha X HUGO:ITGAX hgnc_id:HGNC:6152 HGNC:6152 ENTREZ:3687 UNIPROT:P20702 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:MARKERS_DC Maps_Modules_end References_begin: PMID:15573129 CD11c is a maker of myeloid DCs. PMID:8920882 FLT3 ligand upregulates surface expression of CD11c in DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD11c*"/> <bbox w="80.0" h="50.0" x="6040.0" y="3062.5"/> <glyph class="unit of information" id="_588950aa-f319-410a-9eed-72d6b24c22df"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6057.5" y="3057.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2014_sa516" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 3 receptor subunit alpha HUGO:IL3RA hgnc_id:HGNC:6012 HGNC:6012 ENTREZ:3563 UNIPROT:P26951 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:MARKERS_DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15573129, PMID:11698286 IL3RA is a maker of plasmacytoid DCs (pDCs). For survival in vitro, myeloid DCs are dependent on GM-CSF, whereas pDCs are dependent on IL-3 and IFNA. PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL3RA"/> <bbox w="80.0" h="50.0" x="6040.0" y="2992.5"/> <glyph class="unit of information" id="_4d3efaf5-b4d4-41e4-8fcb-d077038f5980"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6057.5" y="2987.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2015_sa967"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: vascular endothelial growth factor A HUGO:VEGFA hgnc_id:HGNC:12680 HGNC:12680 ENTREZ:7422 UNIPROT:P15692 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15573129, PMID:8837607 Vascular endothelial growth factor (VEGF) was the first tumour-derived factor shown to inhibit DC differentiation. The involvement of VEGF in tumour-induced defects in DC differentiation was indicated by in vitro experiments in which neutralizing VEGF-specific antibody abrogated the negative effect of tumour-cell-conditioned medium on the differentiation of DCs from HPCs. (VEGF) inhibit the activation of NF-B by blocking IB phosphorylation55, 101, 102, possibly through activation of STAT3 (signal transducer and activator of transcription 3). Recent data have shown that STAT3 might also bind p65 subunits of NF-B, thereby directly inhibiting NF-B activity PMID:9570538 VEGF inhibits TNF-α inducible activation of NF-κB in HPC, resulting in inhibition of DC differentiation PMID:16002046 Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="VEGFA"/> <bbox w="80.0" h="40.0" x="40.0" y="2215.0"/> </glyph> <glyph class="macromolecule" id="s2018_sa520" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 3 HUGO:SOCS3 hgnc_id:HGNC:19391 HGNC:19391 ENTREZ:9021 UNIPROT:O14543 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). SOCS proteins are characterized by the presence of an Src homology 2 domain and a C-terminal conserved domain called the SOCS box, and their inhibitory effects derive from direct interaction with cytokine receptors and/or Janus kinases (JAKs), thereby preventing recruitment of STATs to the signaling complex References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS3"/> <bbox w="80.0" h="40.0" x="4775.0" y="1680.0"/> </glyph> <glyph class="macromolecule" id="s2019_sa521"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: fms related tyrosine kinase 3 ligand HUGO:FLT3LG hgnc_id:HGNC:3766 HGNC:3766 ENTREZ:2323 UNIPROT:P49771 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10477595, PMID:9268501, PMID:8920882 The cytokine FLT3 ligand (FL) enhances dendritic cell (DC) generation and differentiation. PMID:10477595 FL induces Ag-presenting ability of DCs. FL induced a high level of NF-κB nuclear translocation and specific DNA binding VEGF inhibited FL-inducible activation of transcription factor NF-κB. PMID:14670306 STAT3 is required for Flt3L-dependent dendritic cell differentiation. 9176488 Flt3L treatment not only induced complete tumor regression in a significant proportion of mice, but also decreased tumor growth rate in the remaining mice. Probabli via DC activation. PMID:16418395 Activation of the Flt3 signal transduction cascade rescues and enhances type I interferon-producing and dendritic cell development. PMID:8920882 Daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers-class II MHC, CD11c, DEC205, and CD86. FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. PMID:25215878 FLT3L partially antagonized IL-10-mediated inhibition on DCs function and downregulates IL10 mRNA expression in DCs PMID:10477595, PMID:8920882, PMID:25215878 FLT3L induces Ag-presenting ability of Dcs. Probably via induction of surface expression of class II MHC and CD86 and also expression of CD83, a and CD80 and was significantly enhanced by the FLT3L Daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers CD11c, DEC205. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT3LG"/> <bbox w="80.0" h="40.0" x="3915.0" y="150.0"/> </glyph> <glyph class="macromolecule" id="s2020_sa522" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 10 HUGO:TNFSF10 hgnc_id:HGNC:11925 HGNC:11925 ENTREZ:8743 UNIPROT:P50591 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:11823516 Human immature dendritic cells express on their cell surface four different cytotoxic TNF family ligands: TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis inducing ligand; while cancer cells express the corresponding death receptors. Disruptions of interactions between the four ligands expressed on DCs and corresponding death-signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion proteins block the cytotoxic activity of DCs directed against cancer cells. PMID:10811870 I IFN induces TRAIL mRNA expression in DCs and enhances apoptosis of target tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAIL*"/> <bbox w="80.0" h="40.0" x="3395.0" y="3420.0"/> </glyph> <glyph class="macromolecule" id="s2021_sa523" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Fas ligand HUGO:FASLG hgnc_id:HGNC:11936 HGNC:11936 ENTREZ:356 UNIPROT:P48023 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:11823516 Human immature dendritic cells express on their cell surface four different cytotoxic TNF family ligands: TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis inducing ligand; while cancer cells express the corresponding death receptors. Disruptions of interactions between the four ligands expressed on DCs and corresponding death-signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion proteins block the cytotoxic activity of DCs directed against cancer cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FASL*"/> <bbox w="80.0" h="40.0" x="3475.0" y="3420.0"/> </glyph> <glyph class="macromolecule" id="s2022_sa524" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:11238627 TNF induces p38 signaling and downstream expression of CD1a, CD40, CD80, CD86, HLA-DR, and CD83 References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: tumor necrosis factor HUGO:TNF hgnc_id:HGNC:11892 HGNC:11892 ENTREZ:7124 UNIPROT:P01375 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12391186 Maturation of monocyte-derived DCs was induced by TNF-α The surface levels of MHC class II increased markedly after TNF-α stimulation on CD83+ DC In contrast to the striking increase in surface expression of MHC class II, the cell surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:12928370 TNF, but not IL-1, induce monocytes to become DCs despite the presence of fibroblasts. TNF converts activated monocytes/early Mφ into DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNF"/> <bbox w="80.0" h="40.0" x="5285.0" y="1880.0"/> </glyph> <glyph class="phenotype" id="s2023_sa525"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:23510023 RODENT Recently, in an effort to unravel the regulatory signaling pathways involved in the regulation of mouse bone marrow-derived DC cytotoxic function we have partly deconstructed the molecular machinery controlling iNOS in DC generated with GM-CSF and IL-4 (IL-4 DC) or IL-15 (IL-15 DC). We demonstrated that LPS-induced iNOS expression required the activation of the transcription factors NF-κB and ISGF3 only in IL-15 DC and that distinct signaling pathways such as AP-1 may be required in IL-4 DC. IFN-γ induced iNOS expression in IL-4 DC by a STAT-1 dependent mechanism. However in IL-15 DC, the cooperation of PIAS-1 and STAT-3 prevented iNOS expression in response to IFN-γ stimulation HUMAN The mechanisms of cancer cell killing primarily involved the death receptor ligands, perforin/granzyme B and NO. Recent studies have further highlighted the possibility that human pDC producting type I interferons may also function as tumor cell killers.117 Immature CD4+HLA-DR+Lin− DC have also been shown to trigger apoptosis of different cancer cells, but not normal cells, by four different TNF family member ligands (TRAIL, TNF, FasL, and Lymphotoxin (LT)-α1β2) PMID:24777831 Cytotoxic DCs are more efficient than noncytotoxic DCs at activating T cells References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumoricidal_activity"/> <bbox w="430.0" h="155.0" x="3615.0" y="4007.5"/> </glyph> <glyph class="macromolecule" id="s2025_sa527" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: lymphotoxin beta HUGO:LTB hgnc_id:HGNC:6711 HGNC:6711 ENTREZ:4050 UNIPROT:Q06643 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11823516 Human immature dendritic cells express on their cell surface four different cytotoxic TNF family ligands: TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis inducing ligand; while cancer cells express the corresponding death receptors. Disruptions of interactions between the four ligands expressed on DCs and corresponding death-signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion proteins block the cytotoxic activity of DCs directed against cancer cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LTB"/> <bbox w="80.0" h="40.0" x="3655.0" y="3420.0"/> </glyph> <glyph class="macromolecule" id="s2026_sa528"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 23 subunit alpha HUGO:IL23A hgnc_id:HGNC:15488 HGNC:15488 ENTREZ:51561 UNIPROT:Q9NPF7 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:22313874 Tumor-associated DC produce IL-23 which reduces tumor infiltration of CD8+ T cells and suppresses NK cell cytotoxicity References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL23A"/> <bbox w="80.0" h="40.0" x="1535.0" y="3510.0"/> </glyph> <glyph class="macromolecule" id="s2027_sa529" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 23 subunit alpha HUGO:IL23A hgnc_id:HGNC:15488 HGNC:15488 ENTREZ:51561 UNIPROT:Q9NPF7 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:22313874 Tumor-associated DC produce IL-23 which reduces tumor infiltration of CD8+ T cells and suppresses NK cell cytotoxicity References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL23A"/> <bbox w="80.0" h="40.0" x="1735.0" y="2670.0"/> </glyph> <glyph class="macromolecule" id="s2028_sa530" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 HUGO:IL6 hgnc_id:HGNC:6018 HGNC:6018 ENTREZ:3569 UNIPROT:P05231 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15573129, PMID:8837607, PMID:9845545 Macrophage colony-stimulating factor (M-CSF) and IL-6 have also been reported to be involved in the tumour-mediated regulation of DC differentiation. PMID:15356132 The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:11306493 The presence of high (>400 pg/ml) concentrations of IL-6 and M-CSF in tumor cell supernatant was strongly correlated with the inhibitory capacity of tumor cell medium on MO-DC differentiation PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6"/> <bbox w="80.0" h="40.0" x="1455.0" y="2640.0"/> </glyph> <glyph class="macromolecule" id="s2029_sa531" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-type lectin domain family 4 member C HUGO:CLEC4C hgnc_id:HGNC:13258 HGNC:13258 ENTREZ:170482 UNIPROT:Q8WTT0 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:22437871 CLEC4C (CD303), CD1C and THBD (CD141) are the markers of human DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CLEC4C"/> <bbox w="80.0" h="50.0" x="6135.0" y="2935.0"/> <glyph class="unit of information" id="_9edc2287-c77c-4e02-b6da-30aff674a185"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6152.5" y="2930.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2031_sa534" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD1c molecule HUGO:CD1C hgnc_id:HGNC:1636 HGNC:1636 ENTREZ:911 UNIPROT:P29017 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:22437871 CLEC4C (CD303), CD1C and THBD (CD141) are the markers of human DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1C"/> <bbox w="80.0" h="50.0" x="6355.0" y="2935.0"/> <glyph class="unit of information" id="_3c1a0361-bca5-4fb5-b056-a93932f73fd0"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6372.5" y="2930.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2032_sa535" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: thrombomodulin HUGO:THBD hgnc_id:HGNC:11784 HGNC:11784 ENTREZ:7056 UNIPROT:P07204 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:22437871 CLEC4C (CD303), CD1C and THBD (CD141) are the markers of human DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="THBD"/> <bbox w="80.0" h="50.0" x="6445.0" y="2935.0"/> <glyph class="unit of information" id="_e54e5dba-ccfc-4560-b0d9-ccb4ed2f4f9f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6462.5" y="2930.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2034_sa536" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: catenin beta 1 HUGO:CTNNB1 hgnc_id:HGNC:2514 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:24023259 β-Catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8+ T cells PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming,β-catenin enhanced IL-10 induction through mTOR pathway. β-Catenin up-regulates level of mTOR in DCs and activates mTOR signaling. PMID:20705860 β-catenin signaling in DCs is required to induce Treg cells and suppress TH1/TH17 responses. β-catenin signaling in intestinal DCs promotes the expression of Raldh and suppresses the expression of proinflammatory cytokines (IL6, IL23a,IL12p40) but induces IL10 production. PMID:15001769, PMID:17936032 GSK3B phosphorylates beta-catenin and inhibits its activity. Beta-catenin signaling prevents production of inflammatory cytokines IL6, IL-1α, IL-6, TNF-α, and IL-12 p40, But upregulates CCR7, both at the mRNA level and on the plasma membrane. CCR7 is a chemokine receptor important for the migration of DCs from the periphery to T cell areas of lymph nodes. DCs matured by CD activation of beta-catenin signaling alone failed to prime CD4 T cells to produce IFN-γ but did generate high levels of IL10 (Fig. 6A) together with other cytokines (not shown) consistent with type I regulatory T cells References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="β-Catenin*"/> <bbox w="80.0" h="40.0" x="2915.0" y="1210.0"/> <glyph class="state variable" id="_4c1f9c7d-8db8-4430-9669-3150b2b456a5"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="2907.5" y="1225.0"/> </glyph> </glyph> <glyph class="source and sink" id="s2035_sa537" compartmentRef="c2_ca2"> <label text="sa536_degraded"/> <bbox w="30.0" h="30.0" x="2960.0" y="1125.0"/> </glyph> <glyph class="complex" id="s2038_csa94" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:E-Cadherin*:_alpha_-Catenin*:_beta_-Catenin* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:17936032, PMID:22174153 Disruption of E-cadherin-mediated contacts induce DC maturation. It activates a β-catenin-TCF/LEF signaling pathway independent of TLR signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2038"/> <bbox w="130.0" h="180.0" x="1160.0" y="1010.0"/> <glyph class="macromolecule" id="s2036_sa538"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: cadherin 1 HUGO:CDH1 hgnc_id:HGNC:1748 HGNC:1748 ENTREZ:999 UNIPROT:P12830 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17936032, PMID:22174153 Disruption of E-cadherin-mediated contacts induce DC maturation. It activates a β-catenin-TCF/LEF signaling pathway independent of TLR signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="E-Cadherin*"/> <bbox w="80.0" h="40.0" x="1170.0" y="1020.0"/> </glyph> <glyph class="macromolecule" id="s2037_sa539"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: catenin beta 1 HUGO:CTNNB1 hgnc_id:HGNC:2514 HGNC:2514 ENTREZ:1499 UNIPROT:P35222 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:24023259 β-Catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8+ T cells PMID:25730849 L-10 Mediates β-Catenin–Dependent Inhibition of Cross-Priming,β-catenin enhanced IL-10 induction through mTOR pathway. β-Catenin up-regulates level of mTOR in DCs and activates mTOR signaling. PMID:20705860 β-catenin signaling in DCs is required to induce Treg cells and suppress TH1/TH17 responses. β-catenin signaling in intestinal DCs promotes the expression of Raldh and suppresses the expression of proinflammatory cytokines (IL6, IL23a,IL12p40) but induces IL10 production. PMID:15001769, PMID:17936032 GSK3B phosphorylates beta-catenin and inhibits its activity. Beta-catenin signaling prevents production of inflammatory cytokines IL6, IL-1α, IL-6, TNF-α, and IL-12 p40, But upregulates CCR7, both at the mRNA level and on the plasma membrane. CCR7 is a chemokine receptor important for the migration of DCs from the periphery to T cell areas of lymph nodes. DCs matured by CD activation of beta-catenin signaling alone failed to prime CD4 T cells to produce IFN-γ but did generate high levels of IL10 (Fig. 6A) together with other cytokines (not shown) consistent with type I regulatory T cells References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="β-Catenin*"/> <bbox w="80.0" h="40.0" x="1180.0" y="1120.0"/> <glyph class="state variable" id="_7d8136ef-2c2e-4239-a63a-d48dfe27ab1e"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="1175.0" y="1135.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2040_sa541"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: catenin alpha 1 HUGO:CTNNA1 hgnc_id:HGNC:2509 HGNC:2509 ENTREZ:1495 UNIPROT:P35221 catenin alpha 2 HUGO:CTNNA2 hgnc_id:HGNC:2510 HGNC:2510 ENTREZ:1496 UNIPROT:P26232 catenin alpha 3 HUGO:CTNNA3 hgnc_id:HGNC:2511 HGNC:2511 ENTREZ:29119 UNIPROT:Q9UI47 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17936032 Disruption of E-cadherin-mediated contacts induce DC maturation. It activates a β-catenin-TCF/LEF signaling pathway independent of TLR signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="α-Catenin*"/> <bbox w="80.0" h="40.0" x="1170.0" y="1070.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2039_sa540" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: cadherin 1 HUGO:CDH1 hgnc_id:HGNC:1748 HGNC:1748 ENTREZ:999 UNIPROT:P12830 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17936032, PMID:22174153 Disruption of E-cadherin-mediated contacts induce DC maturation. It activates a β-catenin-TCF/LEF signaling pathway independent of TLR signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="E-Cadherin*"/> <bbox w="80.0" h="40.0" x="1125.0" y="1270.0"/> </glyph> <glyph class="macromolecule" id="s2041_sa542" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: catenin alpha 1 HUGO:CTNNA1 hgnc_id:HGNC:2509 HGNC:2509 ENTREZ:1495 UNIPROT:P35221 catenin alpha 2 HUGO:CTNNA2 hgnc_id:HGNC:2510 HGNC:2510 ENTREZ:1496 UNIPROT:P26232 catenin alpha 3 HUGO:CTNNA3 hgnc_id:HGNC:2511 HGNC:2511 ENTREZ:29119 UNIPROT:Q9UI47 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:17936032 Disruption of E-cadherin-mediated contacts induce DC maturation. It activates a β-catenin-TCF/LEF signaling pathway independent of TLR signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="α-Catenin*"/> <bbox w="80.0" h="40.0" x="1125.0" y="1220.0"/> </glyph> <glyph class="nucleic acid feature" id="s2042_sa543" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine receptor 7 HUGO:CCR7 hgnc_id:HGNC:1608 HGNC:1608 ENTREZ:1236 UNIPROT:P32248 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17936032 Beta-catenin signaling upregulates CCR7, both at the mRNA level and on the plasma membrane. CCR7 is a chemokine receptor important for the migration of DCs from the periphery to T cell areas of lymph node References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCR7"/> <bbox w="70.0" h="25.0" x="2800.0" y="1017.5"/> </glyph> <glyph class="nucleic acid feature" id="s2043_sa544" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine receptor 7 HUGO:CCR7 hgnc_id:HGNC:1608 HGNC:1608 ENTREZ:1236 UNIPROT:P32248 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17936032 Beta-catenin signaling upregulates CCR7, both at the mRNA level and on the plasma membrane. CCR7 is a chemokine receptor important for the migration of DCs from the periphery to T cell areas of lymph node References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCR7"/> <bbox w="90.0" h="25.0" x="2790.0" y="947.5"/> <glyph class="unit of information" id="_e4b99c84-af7e-4d25-95b7-395c1fba6754"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="2825.0" y="942.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2046_sa73" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <bbox w="80.0" h="40.0" x="6435.0" y="2100.0"/> <glyph class="state variable" id="_3494a511-b2b8-474f-a467-c95361b097fd"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6430.0" y="2115.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s310_sa555"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 13 HUGO:IL13 hgnc_id:HGNC:5973 HGNC:5973 ENTREZ:3596 UNIPROT:P35225 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:11306493, PMID:12244147 Both IL-4 and IL-13 reverse the inhibitory effects of renal cell carcinoma conditioned media (RCC CM) or IL-6+M-CSF on the phenotypic and functional differentiation of CD34+ into DCs. L-4R type II signaling downstream of IL4 andIL13 is sufficient to promote DC maturation at low doses of GM-CSF References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL13"/> <bbox w="80.0" h="40.0" x="7275.0" y="2440.0"/> </glyph> <glyph class="complex" id="s620_csa97" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL13:IL13RA1:IL4R:JAK1:JAK2:TYK2 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:14610620 IL13 acts via IL4 receptor type 2, which contains two subunits IL4R and IL13RA1 JAK1 associated with IL4R and JAK2 or TYK associated with IL13RA1 participate in signal transduction; They phosphorylate the second, third, or fourth tyrosine residues of the IL-4Ra cytoplasmic domain. PMID:12244147 IL-4R type II signaling downstream of IL4 andIL13 is sufficient to promote DC maturation at low doses of GM-CSF. The proportions of mature DC represented by high surface expression of MHC class II (MHC II) and CD86 as well as CD80, CD40, and CD54 (data not shown) IL-4R type II signaling acts probably via STAT6. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL13/Receptor-TYPE_2"/> <bbox w="290.5" h="170.0" x="6509.75" y="2545.0"/> <glyph class="macromolecule" id="s315_sa557"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <bbox w="80.0" h="40.0" x="6700.25" y="2645.0"/> <glyph class="state variable" id="_f8e4dd73-ca75-49ed-a279-ff477937a4b2"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6692.75" y="2660.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s316_sa558"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: tyrosine kinase 2 HUGO:TYK2 hgnc_id:HGNC:12440 HGNC:12440 ENTREZ:7297 UNIPROT:P29597 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 TYK2 is a member of the Janus kinase family. TYK2 associated with IL13RA1 participates in signal transduction. PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TYK2"/> <bbox w="80.0" h="40.0" x="6700.25" y="2605.0"/> <glyph class="state variable" id="_2548b371-493b-475f-95e6-18d1263b3213"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6692.75" y="2620.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s339_sa559"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 4 receptor HUGO:IL4R hgnc_id:HGNC:6015 HGNC:6015 ENTREZ:3566 UNIPROT:P24394 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL4R"/> <bbox w="80.0" h="50.0" x="6600.25" y="2570.0"/> <glyph class="state variable" id="_7c820337-10ea-483d-840d-85bf9cfdbc2c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6672.75" y="2604.3892"/> </glyph> <glyph class="unit of information" id="_15deb1f0-be75-4dbf-bdd6-c804434cf80a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6617.75" y="2565.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s340_sa560"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 13 receptor subunit alpha 1 HUGO:IL13RA1 hgnc_id:HGNC:5974 HGNC:5974 ENTREZ:3597 UNIPROT:P78552 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620, PMID:12223527 IL13 acts via IL4 receptor type 2, which contains two subunits IL4R and IL13RA1 PMID:10358772, PMID:12244147 IL-4 mediates its effect through the type I IL-4R, composed of the IL-4Rα and common gamma-chain (IL-2Rγ); And, probably through type II IL-4R is composed of the IL-4Ra chain and IL-13Ra1 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL13RA1"/> <bbox w="80.0" h="50.0" x="6600.25" y="2620.0"/> <glyph class="state variable" id="_b662dacd-6c7a-4829-94aa-76acee6fed1a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6672.75" y="2653.7566"/> </glyph> <glyph class="unit of information" id="_d51e395a-5063-4080-9231-4adda7a9e104"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6617.75" y="2615.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s337_sa561"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 13 HUGO:IL13 hgnc_id:HGNC:5973 HGNC:5973 ENTREZ:3596 UNIPROT:P35225 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:11306493, PMID:12244147 Both IL-4 and IL-13 reverse the inhibitory effects of renal cell carcinoma conditioned media (RCC CM) or IL-6+M-CSF on the phenotypic and functional differentiation of CD34+ into DCs. L-4R type II signaling downstream of IL4 andIL13 is sufficient to promote DC maturation at low doses of GM-CSF References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL13"/> <bbox w="80.0" h="40.0" x="6520.25" y="2595.0"/> </glyph> <glyph class="macromolecule" id="s386_sa562"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="6700.25" y="2565.0"/> <glyph class="state variable" id="_7c1af755-6d9a-482b-8940-da66fa178594"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6695.25" y="2580.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2049_sa565" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 6 HUGO:STAT6 hgnc_id:HGNC:11368 HGNC:11368 ENTREZ:6778 UNIPROT:P42226 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12244147 IL-4R type II signaling downstream of IL4 andIL13 is sufficient to promote DC maturation at low doses of GM-CSF. The proportions of mature DC represented by high surface expression of MHC class II (MHC II) and CD86 as well as CD80, CD40, and CD54 (data not shown) IL-4R type II signaling acts probably via STAT6. Enhancement of IL-12 p70 production is mediated by IL-4, but not IL-13, through IL-4R type I and depends on JAK3 and STAT6 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 PMID:25582338 Activated STAT6 levels were significantly increased in IL-4 DCs as compared with IL-15 DCs. PMID:14764699 STAT6 is preferentially activated in differentiating DCs and declines as the cells mature PMID:20231889 After LPS stimulation and Stat6−/− BMDCs showed significant lower capacity to secret TNFα and IL-12, although we observed relatively higher levels of TNFα in Stat6−/− BMDCs in the unstimulated condition References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT6"/> <bbox w="80.0" h="40.0" x="6355.0" y="2310.0"/> <glyph class="state variable" id="_6cac218b-83d0-48d6-a997-239b4c8fe98d"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6350.0" y="2325.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2050_sa566" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 6 HUGO:STAT6 hgnc_id:HGNC:11368 HGNC:11368 ENTREZ:6778 UNIPROT:P42226 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12244147 IL-4R type II signaling downstream of IL4 andIL13 is sufficient to promote DC maturation at low doses of GM-CSF. The proportions of mature DC represented by high surface expression of MHC class II (MHC II) and CD86 as well as CD80, CD40, and CD54 (data not shown) IL-4R type II signaling acts probably via STAT6. Enhancement of IL-12 p70 production is mediated by IL-4, but not IL-13, through IL-4R type I and depends on JAK3 and STAT6 PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 PMID:25582338 Activated STAT6 levels were significantly increased in IL-4 DCs as compared with IL-15 DCs. PMID:14764699 STAT6 is preferentially activated in differentiating DCs and declines as the cells mature PMID:20231889 After LPS stimulation and Stat6−/− BMDCs showed significant lower capacity to secret TNFα and IL-12, although we observed relatively higher levels of TNFα in Stat6−/− BMDCs in the unstimulated condition References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT6"/> <bbox w="80.0" h="40.0" x="6145.0" y="2310.0"/> <glyph class="state variable" id="_0c423522-4d8d-4830-b93e-1cf043742c1a"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6137.5" y="2325.0"/> </glyph> </glyph> <glyph class="complex" id="s2051_csa99" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL12p35*:IL12p40* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: 10993913 Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12p70 production by mouse and human dendritic cells. 11702064 IL15 signaling is important for IL12 production 15851485 Type I interferon signaling involed in interleukin-12p70 secretion by dendritic cells 14607893 Induction of IL-12p70 downstream of TLR4 is enhanced by p38 and JNK1/2 signaling, and suppressed by ERK1/2 signaling; References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p70"/> <bbox w="100.0" h="130.0" x="5455.0" y="2265.0"/> <glyph class="macromolecule" id="s2053_sa567"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12A HUGO:IL12A hgnc_id:HGNC:5969 HGNC:5969 ENTREZ:3592 UNIPROT:P29459 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p35*"/> <bbox w="80.0" h="40.0" x="5465.0" y="2320.0"/> </glyph> <glyph class="macromolecule" id="s2052_sa569"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12B HUGO:IL12B hgnc_id:HGNC:5970 HGNC:5970 ENTREZ:3593 UNIPROT:P29460 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p40*"/> <bbox w="80.0" h="40.0" x="5465.0" y="2275.0"/> </glyph> </glyph> <glyph class="complex" id="s2054_csa100"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL12p35*:IL12p40* Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10993913 Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12p70 production by mouse and human dendritic cells. PMID:25446896 IL-10 Blocks CD8+ T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells PMID:21042762 Inhibition of TGF-ß signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs. Smad2/3 somehow suppresses IRF3 phosphorylation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p70"/> <bbox w="100.0" h="130.0" x="6685.0" y="3165.0"/> <glyph class="macromolecule" id="s2055_sa570"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12A HUGO:IL12A hgnc_id:HGNC:5969 HGNC:5969 ENTREZ:3592 UNIPROT:P29459 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p35*"/> <bbox w="80.0" h="40.0" x="6695.0" y="3225.0"/> </glyph> <glyph class="macromolecule" id="s2056_sa571"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 12B HUGO:IL12B hgnc_id:HGNC:5970 HGNC:5970 ENTREZ:3593 UNIPROT:P29460 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:18492954 TLR4 signaling induces IL12 expression in DC. This expression is downregulated by IL10. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL12p40*"/> <bbox w="80.0" h="40.0" x="6695.0" y="3175.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2057_sa572" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 23 subunit alpha HUGO:IL23A hgnc_id:HGNC:15488 HGNC:15488 ENTREZ:51561 UNIPROT:Q9NPF7 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL23A"/> <bbox w="90.0" h="25.0" x="1729.0" y="2568.75"/> <glyph class="unit of information" id="_d583562b-09fc-4e24-88bb-4e4696a94b52"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="1764.0" y="2563.75"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2058_sa573" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 23 subunit alpha HUGO:IL23A hgnc_id:HGNC:15488 HGNC:15488 ENTREZ:51561 UNIPROT:Q9NPF7 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL23A"/> <bbox w="70.0" h="25.0" x="1740.0" y="2468.75"/> </glyph> <glyph class="nucleic acid feature" id="s2059_sa574" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibin beta A subunit HUGO:INHBA hgnc_id:HGNC:6066 HGNC:6066 ENTREZ:3624 UNIPROT:P08476 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="INHBA"/> <bbox w="70.0" h="25.0" x="1600.0" y="2467.5"/> </glyph> <glyph class="nucleic acid feature" id="s2060_sa575" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibin beta A subunit HUGO:INHBA hgnc_id:HGNC:6066 HGNC:6066 ENTREZ:3624 UNIPROT:P08476 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="INHBA"/> <bbox w="90.0" h="25.0" x="1590.0" y="2557.5"/> <glyph class="unit of information" id="_a20f720a-fc9f-4f05-bd3d-ee3e90fa6449"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="1625.0" y="2552.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2061_sa576" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibin beta A subunit HUGO:INHBA hgnc_id:HGNC:6066 HGNC:6066 ENTREZ:3624 UNIPROT:P08476 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="INHBA"/> <bbox w="80.0" h="40.0" x="1595.0" y="2640.0"/> </glyph> <glyph class="macromolecule multimer" id="s2062_sa577" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibin beta A subunit HUGO:INHBA hgnc_id:HGNC:6066 HGNC:6066 ENTREZ:3624 UNIPROT:P08476 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="INHBA"/> <bbox w="86.0" h="46.0" x="1602.0" y="2747.0"/> <glyph class="unit of information" id="_55bb9d26-21df-4f41-b6f0-a9619af7dddf"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="1635.0" y="2742.0"/> </glyph> </glyph> <glyph class="macromolecule multimer" id="s2063_sa578"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibin beta A subunit HUGO:INHBA hgnc_id:HGNC:6066 HGNC:6066 ENTREZ:3624 UNIPROT:P08476 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24204259 IL-4Rα-deficient DCs produced reduced IL-12, and IL18 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and INHBA (activin A), cytokines previously implicated in promoting Th2 responses. probably via STAT6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="INHBA"/> <bbox w="86.0" h="46.0" x="1432.0" y="3497.0"/> <glyph class="unit of information" id="_5e01b0cf-add9-4c9f-99fa-fee4aa9a5dea"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="1465.0" y="3492.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s545_sa579"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 1 HUGO:CSF1 hgnc_id:HGNC:2432 HGNC:2432 ENTREZ:1435 UNIPROT:P09603 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:9845545 Macrophage colony-stimulating factor (M-CSF) and IL-6 have also been reported to be involved in the tumour-mediated regulation of DC differentiation. PMID:15573129, PMID:8837607, PMID:9845545 PMID:11306493 IL4 signaling blocks CSF (M-CSF) production in DC induced by tumor cells. The presence of high (>400 pg/ml) concentrations of IL-6 and M-CSF in tumor cell supernatant was strongly correlated with the inhibitory capacity of tumor cell medium on MO-DC differentiation References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1"/> <bbox w="80.0" h="40.0" x="1855.0" y="310.0"/> </glyph> <glyph class="macromolecule" id="s575_sa580" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 1 receptor HUGO:CSF1R hgnc_id:HGNC:2433 HGNC:2433 ENTREZ:1436 UNIPROT:P07333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:10705574 CSF1 acts via CSF1R PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1R"/> <bbox w="80.0" h="50.0" x="2155.0" y="755.0"/> <glyph class="unit of information" id="_943273ba-da1f-4994-9882-24d42db83630"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2172.5" y="750.0"/> </glyph> </glyph> <glyph class="complex" id="s591_csa101" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CSF1:CSF1R Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10705574 CSF1 acts via CSF1R References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s591"/> <bbox w="100.0" h="120.0" x="2025.0" y="570.0"/> <glyph class="macromolecule" id="s593_sa581"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 1 HUGO:CSF1 hgnc_id:HGNC:2432 HGNC:2432 ENTREZ:1435 UNIPROT:P09603 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:9845545 Macrophage colony-stimulating factor (M-CSF) and IL-6 have also been reported to be involved in the tumour-mediated regulation of DC differentiation. PMID:15573129, PMID:8837607, PMID:9845545 PMID:11306493 IL4 signaling blocks CSF (M-CSF) production in DC induced by tumor cells. The presence of high (>400 pg/ml) concentrations of IL-6 and M-CSF in tumor cell supernatant was strongly correlated with the inhibitory capacity of tumor cell medium on MO-DC differentiation References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1"/> <bbox w="80.0" h="40.0" x="2035.0" y="580.0"/> </glyph> <glyph class="macromolecule" id="s592_sa582"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 1 receptor HUGO:CSF1R hgnc_id:HGNC:2433 HGNC:2433 ENTREZ:1436 UNIPROT:P07333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:10705574 CSF1 acts via CSF1R PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1R"/> <bbox w="80.0" h="50.0" x="2035.0" y="625.0"/> <glyph class="unit of information" id="_e0de52c6-5377-44d8-8083-e7e7b50f60c3"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2052.5" y="620.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s128_csa102" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL6R:gp130* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6R"/> <bbox w="123.25" h="133.625" x="2373.375" y="503.1875"/> <glyph class="macromolecule" id="s131_sa583"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 6 signal transducer HUGO:IL6ST hgnc_id:HGNC:6021 HGNC:6021 ENTREZ:3572 UNIPROT:P40189 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="gp130*"/> <bbox w="80.0" h="50.0" x="2395.0" y="565.0"/> <glyph class="state variable" id="_bba3f917-fad4-488f-a3e1-bbf9037fd430"> <state value="P" variable="Y759"/> <bbox w="35.0" h="10.0" x="2457.5" y="562.541"/> </glyph> <glyph class="unit of information" id="_f02c6d97-dddc-48d3-b24d-a33f3752b433"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2412.5" y="560.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s130_sa584"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 6 receptor HUGO:IL6R hgnc_id:HGNC:6019 HGNC:6019 ENTREZ:3570 UNIPROT:P08887 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:12754507, PMID:24418198 SOCS3 binds with high affinity to the phosphorylated Tyr759 (Y759) Of gp130 to suppress IL-6 signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6R"/> <bbox w="80.0" h="50.0" x="2396.625" y="518.1875"/> <glyph class="unit of information" id="_3f304f9d-df9e-4d01-81f4-522adfafebb2"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2414.125" y="513.1875"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s2069_csa103" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL6:IL6R:gp130* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6R"/> <bbox w="160.0" h="191.40625" x="2185.0" y="474.29688"/> <glyph class="macromolecule" id="s2070_sa586"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 6 signal transducer HUGO:IL6ST hgnc_id:HGNC:6021 HGNC:6021 ENTREZ:3572 UNIPROT:P40189 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="gp130*"/> <bbox w="80.0" h="50.0" x="2225.0" y="580.7031"/> <glyph class="state variable" id="_dd5bb8e3-ca1f-442d-b5bc-30039da531cd"> <state value="P" variable="Y759"/> <bbox w="35.0" h="10.0" x="2287.5" y="578.24414"/> </glyph> <glyph class="unit of information" id="_8ab15a7b-c7ce-4836-b49b-41fd6f89592c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2242.5" y="575.7031"/> </glyph> </glyph> <glyph class="macromolecule" id="s2071_sa587"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 6 receptor HUGO:IL6R hgnc_id:HGNC:6019 HGNC:6019 ENTREZ:3570 UNIPROT:P08887 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:12754507, PMID:24418198 SOCS3 binds with high affinity to the phosphorylated Tyr759 (Y759) Of gp130 to suppress IL-6 signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6R"/> <bbox w="80.0" h="50.0" x="2225.0" y="530.7031"/> <glyph class="unit of information" id="_e31f3263-124e-4770-a469-21e075300c59"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2242.5" y="525.7031"/> </glyph> </glyph> <glyph class="macromolecule" id="s2068_sa588"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 6 HUGO:IL6 hgnc_id:HGNC:6018 HGNC:6018 ENTREZ:3569 UNIPROT:P05231 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15573129, PMID:8837607, PMID:9845545 Macrophage colony-stimulating factor (M-CSF) and IL-6 have also been reported to be involved in the tumour-mediated regulation of DC differentiation. PMID:15356132 The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:11306493 The presence of high (>400 pg/ml) concentrations of IL-6 and M-CSF in tumor cell supernatant was strongly correlated with the inhibitory capacity of tumor cell medium on MO-DC differentiation PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6"/> <bbox w="80.0" h="40.0" x="2225.0" y="485.70312"/> </glyph> </glyph> <glyph class="macromolecule" id="s2072_sa589" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 signal transducer HUGO:IL6ST hgnc_id:HGNC:6021 HGNC:6021 ENTREZ:3572 UNIPROT:P40189 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="gp130*"/> <bbox w="80.0" h="50.0" x="2315.0" y="695.0"/> <glyph class="state variable" id="_5efbfd33-86d0-4609-b16b-906606a66eae"> <state value="P" variable="Y759"/> <bbox w="35.0" h="10.0" x="2377.5" y="692.541"/> </glyph> <glyph class="unit of information" id="_d66703f6-91b8-4471-a19f-44cc6b5eee0b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2332.5" y="690.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2073_sa590" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 receptor HUGO:IL6R hgnc_id:HGNC:6019 HGNC:6019 ENTREZ:3570 UNIPROT:P08887 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:12754507, PMID:24418198 SOCS3 binds with high affinity to the phosphorylated Tyr759 (Y759) Of gp130 to suppress IL-6 signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6R"/> <bbox w="80.0" h="50.0" x="2445.0" y="685.0"/> <glyph class="unit of information" id="_fb0459f5-a859-4ed9-9b21-0f775f2a2d9a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2462.5" y="680.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2074_sa591" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 signal transducer HUGO:IL6ST hgnc_id:HGNC:6021 HGNC:6021 ENTREZ:3572 UNIPROT:P40189 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="gp130*"/> <bbox w="80.0" h="50.0" x="2310.0" y="875.0"/> <glyph class="state variable" id="_2cd5e5b5-2c09-4e47-9df4-1a8887668b09"> <state value="P" variable="Y759"/> <bbox w="35.0" h="10.0" x="2372.5" y="872.541"/> </glyph> <glyph class="unit of information" id="_499d579b-2a48-465f-b1c3-d609cdedeb52"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2327.5" y="870.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2075_sa592" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 1 receptor HUGO:CSF1R hgnc_id:HGNC:2433 HGNC:2433 ENTREZ:1436 UNIPROT:P07333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:10705574 CSF1 acts via CSF1R PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1R"/> <bbox w="80.0" h="50.0" x="2170.0" y="915.0"/> <glyph class="unit of information" id="_35425e7b-f82f-4e70-8514-2c8f4f140d34"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2187.5" y="910.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2076_sa593" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 2 receptor alpha subunit HUGO:CSF2RA hgnc_id:HGNC:2435 HGNC:2435 ENTREZ:1438 UNIPROT:P15509 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RA"/> <bbox w="80.0" h="50.0" x="3585.0" y="615.0"/> <glyph class="unit of information" id="_ca35c6d2-7fdb-435f-9de1-012c2625a113"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3602.5" y="610.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2077_sa594" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 2 receptor beta common subunit HUGO:CSF2RB hgnc_id:HGNC:2436 HGNC:2436 ENTREZ:1439 UNIPROT:P32927 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) ( References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RB"/> <bbox w="80.0" h="50.0" x="3705.0" y="625.0"/> <glyph class="unit of information" id="_ee12ff32-eb40-46aa-b440-c9aa8faca251"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3722.5" y="620.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2078_sa595" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 2 receptor alpha subunit HUGO:CSF2RA hgnc_id:HGNC:2435 HGNC:2435 ENTREZ:1438 UNIPROT:P15509 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits PMID:11306493 IL4 signaling prevents CSF2RA(CD116) lost on DC surface in tumor microenviroment. and blocks gp130 and CSF1R (CD115)surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RA"/> <bbox w="80.0" h="50.0" x="3585.0" y="755.0"/> <glyph class="unit of information" id="_2105580b-b430-466c-98d6-e91d4e3ddc88"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3602.5" y="750.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2079_sa596" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 2 receptor beta common subunit HUGO:CSF2RB hgnc_id:HGNC:2436 HGNC:2436 ENTREZ:1439 UNIPROT:P32927 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) ( References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RB"/> <bbox w="80.0" h="50.0" x="3705.0" y="765.0"/> <glyph class="unit of information" id="_ba1a8d56-1308-4a3f-8dbc-8f3eb4634f91"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3722.5" y="760.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2080_sa597" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 1 HUGO:CSF1 hgnc_id:HGNC:2432 HGNC:2432 ENTREZ:1435 UNIPROT:P09603 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:9845545 Macrophage colony-stimulating factor (M-CSF) and IL-6 have also been reported to be involved in the tumour-mediated regulation of DC differentiation. PMID:15573129, PMID:8837607, PMID:9845545 PMID:11306493 IL4 signaling blocks CSF (M-CSF) production in DC induced by tumor cells. The presence of high (>400 pg/ml) concentrations of IL-6 and M-CSF in tumor cell supernatant was strongly correlated with the inhibitory capacity of tumor cell medium on MO-DC differentiation References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1"/> <bbox w="80.0" h="40.0" x="2060.0" y="1140.0"/> </glyph> <glyph class="macromolecule" id="s2081_sa598"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD40 ligand HUGO:CD40LG hgnc_id:HGNC:11935 HGNC:11935 ENTREZ:959 UNIPROT:P29965 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:11581322 CD40LG induce maturation of DC. PMID:8760829 Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD40LG"/> <bbox w="80.0" h="40.0" x="4905.0" y="3870.0"/> </glyph> <glyph class="complex" id="s2082_csa104" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CD40:CD40LG Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:8760829 Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. PMID:23002440 CD40/CD154 Blockade Inhibits Dendritic Cell Expression of Inflammatory Cytokines PMID:14504095 IL-1β (C) and IL-12p35 transcripts and IL6, TNF secretion. CD40L stimulation induces mRNA espression of p40 and p35 subunits of IL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2082"/> <bbox w="100.0" h="130.0" x="4965.0" y="3515.0"/> <glyph class="macromolecule" id="s2083_sa599"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD40 molecule HUGO:CD40 hgnc_id:HGNC:11919 HGNC:11919 ENTREZ:958 UNIPROT:P25942 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:11964292, PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:8760829 Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD40"/> <bbox w="80.0" h="40.0" x="4975.0" y="3525.0"/> <glyph class="unit of information" id="_38efdcdf-c6ea-4a44-a059-48019f06aa9a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4992.5" y="3520.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2084_sa600"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD40 ligand HUGO:CD40LG hgnc_id:HGNC:11935 HGNC:11935 ENTREZ:959 UNIPROT:P29965 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:11581322 CD40LG induce maturation of DC. PMID:8760829 Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD40LG"/> <bbox w="80.0" h="40.0" x="4975.0" y="3575.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s775_sa601" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence A HUGO:MICA hgnc_id:HGNC:7090 HGNC:7090 ENTREZ:100507436 UNIPROT:Q29983 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICA"/> <bbox w="80.0" h="40.0" x="5795.0" y="1260.0"/> </glyph> <glyph class="nucleic acid feature" id="s967_sa602" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence B HUGO:MICB hgnc_id:HGNC:7091 HGNC:7091 ENTREZ:4277 UNIPROT:Q29980 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICB"/> <bbox w="90.0" h="25.0" x="5900.0" y="1337.5"/> <glyph class="unit of information" id="_ed300a95-a9a0-443f-a9cb-72df47855fd3"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5935.0" y="1332.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s966_sa603" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence A HUGO:MICA hgnc_id:HGNC:7090 HGNC:7090 ENTREZ:100507436 UNIPROT:Q29983 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICA"/> <bbox w="90.0" h="25.0" x="5780.0" y="1337.5"/> <glyph class="unit of information" id="_7098c714-41b1-481a-b346-bff9b455b5a2"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5815.0" y="1332.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s776_sa604" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence B HUGO:MICB hgnc_id:HGNC:7091 HGNC:7091 ENTREZ:4277 UNIPROT:Q29980 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICB"/> <bbox w="80.0" h="40.0" x="5915.0" y="1260.0"/> </glyph> <glyph class="nucleic acid feature" id="s971_sa605" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence B HUGO:MICB hgnc_id:HGNC:7091 HGNC:7091 ENTREZ:4277 UNIPROT:Q29980 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICB"/> <bbox w="70.0" h="25.0" x="5910.0" y="1407.5"/> </glyph> <glyph class="nucleic acid feature" id="s970_sa606" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence A HUGO:MICA hgnc_id:HGNC:7090 HGNC:7090 ENTREZ:100507436 UNIPROT:Q29983 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICA"/> <bbox w="70.0" h="25.0" x="5790.0" y="1407.5"/> </glyph> <glyph class="macromolecule" id="s2085_sa607" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 2 receptor subunit beta HUGO:IL2RB hgnc_id:HGNC:6009 HGNC:6009 ENTREZ:3560 UNIPROT:P14784 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16212621 IL-2- and IL-15-induced phosphorylation of the IL-2RB chain in T cells. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RB"/> <bbox w="80.0" h="50.0" x="6405.0" y="1585.0"/> <glyph class="state variable" id="_c0ae790a-2004-4d78-981b-bb3a9af217c4"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6400.0" y="1605.0"/> </glyph> <glyph class="unit of information" id="_53eff188-a571-4181-b8e9-59d3c7306177"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6422.5" y="1580.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2086_sa608"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence B HUGO:MICB hgnc_id:HGNC:7091 HGNC:7091 ENTREZ:4277 UNIPROT:Q29980 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICB"/> <bbox w="80.0" h="40.0" x="6605.0" y="790.0"/> </glyph> <glyph class="macromolecule" id="s2087_sa609"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: MHC class I polypeptide-related sequence A HUGO:MICA hgnc_id:HGNC:7090 HGNC:7090 ENTREZ:100507436 UNIPROT:Q29983 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14607946 IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MICA"/> <bbox w="80.0" h="40.0" x="6495.0" y="750.0"/> </glyph> <glyph class="complex" id="s1108_csa8" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL15:IL15RA:IL2RB:IL2RG:JAK1:JAK3 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1107"/> <bbox w="195.0" h="180.0" x="6627.5" y="1450.0"/> <glyph class="macromolecule" id="s1106_sa56"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit gamma HUGO:IL2RG hgnc_id:HGNC:6010 HGNC:6010 ENTREZ:3561 UNIPROT:P31785 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RG"/> <bbox w="80.0" h="50.0" x="6735.0" y="1465.0"/> <glyph class="unit of information" id="_86978b07-44c2-4644-b910-7f9f5a0a032c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6752.5" y="1460.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1105_sa55"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit beta HUGO:IL2RB hgnc_id:HGNC:6009 HGNC:6009 ENTREZ:3560 UNIPROT:P14784 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16212621 IL-2- and IL-15-induced phosphorylation of the IL-2RB chain in T cells. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RB"/> <bbox w="80.0" h="50.0" x="6735.0" y="1525.0"/> <glyph class="state variable" id="_b540bba9-5ecd-41d1-a756-90b2e58c7289"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6727.5" y="1545.0"/> </glyph> <glyph class="unit of information" id="_a750afb9-4b97-46bc-93c5-67437e071e2a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6752.5" y="1520.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1104_sa54"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 15 receptor subunit alpha HUGO:IL15RA hgnc_id:HGNC:5978 HGNC:5978 ENTREZ:3601 UNIPROT:Q13261 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15RA"/> <bbox w="80.0" h="50.0" x="6635.0" y="1525.0"/> <glyph class="unit of information" id="_550608c5-f08d-462a-8574-d7e32a668987"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6652.5" y="1520.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2092_sa625"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 15 HUGO:IL15 hgnc_id:HGNC:5977 HGNC:5977 ENTREZ:3600 UNIPROT:P40933 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:7523571 Interleukin 15 (IL-15) controls both the homeostasis and the peripheral activation of natural killer (NK). Interleukin (IL) 15 activates human natural killer cells via components of the IL-2 receptor and induces cytoxic activity against tumor cells and participates in regulation of cytokine production. PMID:17398124, PMID:19913445, PMID:17459805, PMID:21307131 Dendritic cells and macrophages prime natural killer cells by trans-presenting interleukin 15. IL-15 is trans-presented on the surface of IL-15-producing cells in complex with the IL-15 receptor α chain (IL-15Rα). It results in tumoricidal activity of NK cells. PMID:14607946 DCs activate resting NK cells by expressing MHC class I-related chain A and B (MICA/B), ligands for NKG2D, in response to IFN-alpha and IL15. IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15"/> <bbox w="80.0" h="40.0" x="6635.0" y="1470.0"/> </glyph> <glyph class="macromolecule" id="s2095_sa628"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 3 HUGO:JAK3 hgnc_id:HGNC:6193 HGNC:6193 ENTREZ:3718 UNIPROT:P52333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK3"/> <bbox w="80.0" h="40.0" x="6735.0" y="1580.0"/> </glyph> <glyph class="macromolecule" id="s2094_sa629"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="6635.0" y="1580.0"/> <glyph class="state variable" id="_0a70d1d9-51ac-45f3-8633-077044ac21e8"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6630.0" y="1595.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s2088_csa105" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL15:IL15RA Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2088"/> <bbox w="100.0" h="120.0" x="6525.0" y="1010.0"/> <glyph class="macromolecule" id="s2089_sa57"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 15 HUGO:IL15 hgnc_id:HGNC:5977 HGNC:5977 ENTREZ:3600 UNIPROT:P40933 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:7523571 Interleukin 15 (IL-15) controls both the homeostasis and the peripheral activation of natural killer (NK). Interleukin (IL) 15 activates human natural killer cells via components of the IL-2 receptor and induces cytoxic activity against tumor cells and participates in regulation of cytokine production. PMID:17398124, PMID:19913445, PMID:17459805, PMID:21307131 Dendritic cells and macrophages prime natural killer cells by trans-presenting interleukin 15. IL-15 is trans-presented on the surface of IL-15-producing cells in complex with the IL-15 receptor α chain (IL-15Rα). It results in tumoricidal activity of NK cells. PMID:14607946 DCs activate resting NK cells by expressing MHC class I-related chain A and B (MICA/B), ligands for NKG2D, in response to IFN-alpha and IL15. IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15"/> <bbox w="80.0" h="40.0" x="6535.0" y="1020.0"/> </glyph> <glyph class="macromolecule" id="s2090_sa610"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 15 receptor subunit alpha HUGO:IL15RA hgnc_id:HGNC:5978 HGNC:5978 ENTREZ:3601 UNIPROT:Q13261 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15RA"/> <bbox w="80.0" h="50.0" x="6535.0" y="1065.0"/> <glyph class="unit of information" id="_2d9c0f78-f77f-46a0-9943-2f7bed80a501"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6552.5" y="1060.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s1961_sa420" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 15 HUGO:IL15 hgnc_id:HGNC:5977 HGNC:5977 ENTREZ:3600 UNIPROT:P40933 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:7523571 Interleukin 15 (IL-15) controls both the homeostasis and the peripheral activation of natural killer (NK). Interleukin (IL) 15 activates human natural killer cells via components of the IL-2 receptor and induces cytoxic activity against tumor cells and participates in regulation of cytokine production. PMID:17398124, PMID:19913445, PMID:17459805, PMID:21307131 Dendritic cells and macrophages prime natural killer cells by trans-presenting interleukin 15. IL-15 is trans-presented on the surface of IL-15-producing cells in complex with the IL-15 receptor α chain (IL-15Rα). It results in tumoricidal activity of NK cells. PMID:14607946 DCs activate resting NK cells by expressing MHC class I-related chain A and B (MICA/B), ligands for NKG2D, in response to IFN-alpha and IL15. IL-15- and type I IFN-mediated induction of MICA/B in healthy donors is completely inhibited when DCs are incubated in the presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively, suggesting interdependent roles of these cytokines in MICA/B expression. Indeed, DCs produced IL-15 in response to type I IFN, whereas they directly produced IFN-beta, in response to IL-15, which was followed by the production of IFN-alpha. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL15"/> <bbox w="80.0" h="40.0" x="5945.0" y="1690.0"/> </glyph> <glyph class="macromolecule multimer" id="s711_sa611"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon gamma HUGO:IFNG hgnc_id:HGNC:5438 HGNC:5438 ENTREZ:3458 UNIPROT:P01579 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:24777831 IFN-γ induces the cytotoxic function of IL-4 DCs but not IL-15 DCs. iNOS expression was induced by IFN-gamma stimulation in IL4-DC but not in IL15DC via STAT1. PMID:21930769 IFNG/IFNGR1 signaling is required for immune rejection of tumors References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNG"/> <bbox w="86.0" h="46.0" x="4832.0" y="177.0"/> <glyph class="unit of information" id="_13bec8ce-46e6-4cc7-a445-8edcff7aca69"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="4865.0" y="172.0"/> </glyph> </glyph> <glyph class="complex" id="s527_csa106" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IFNGR1:IFNGR2 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: 17683974 IFNG dimer binds to receptor contained two IFNGR1 and two IFNGR2 subunits. 19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2. Ligand engagement of the IFNG receptor leads to activation of receptor-associated Jak1 and Jak2 and phosphorylation of a receptor tyrosine residue (Y440) that serves as a docking site for STAT1, which exists in a latent state in the cytoplasm. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNGR"/> <bbox w="120.0" h="130.0" x="4635.0" y="345.0"/> <glyph class="macromolecule" id="s710_sa612"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon gamma receptor 2 HUGO:IFNGR2 hgnc_id:HGNC:5440 HGNC:5440 ENTREZ:3460 UNIPROT:P38484 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:17683974 IFNG dimer binds to receptor contained two IFNGR1 and two IFNGR2 subunits. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNGR2"/> <bbox w="80.0" h="50.0" x="4655.0" y="400.0"/> <glyph class="unit of information" id="_a7f4bed5-b233-4e12-95cb-12aa95904fa8"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4672.5" y="395.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s709_sa613"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon gamma receptor 1 HUGO:IFNGR1 hgnc_id:HGNC:5439 HGNC:5439 ENTREZ:3459 UNIPROT:P15260 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:17683974 IFNG dimer binds to receptor contained two IFNGR1 and two IFNGR2 subunits. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNGR1"/> <bbox w="80.0" h="50.0" x="4655.0" y="360.0"/> <glyph class="state variable" id="_ed4846e5-8307-405a-82a3-34614ad3c72c"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4650.0" y="379.96017"/> </glyph> <glyph class="unit of information" id="_61167488-76d6-4c1a-925d-2ba967fba580"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4672.5" y="355.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s712_csa107" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IFNG:IFNGR1:IFNGR2:JAK1:JAK2 Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: 17683974 IFNG dimer binds to receptor contained two IFNGR1 and two IFNGR2 subunits. 19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2. Ligand engagement of the IFNG receptor leads to activation of receptor-associated Jak1 and Jak2 and phosphorylation of a receptor tyrosine residue (Y440) that serves as a docking site for STAT1, which exists in a latent state in the cytoplasm. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNGR"/> <bbox w="205.0" h="170.0" x="4652.5" y="495.0"/> <glyph class="macromolecule multimer" id="s717_sa614"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon gamma HUGO:IFNG hgnc_id:HGNC:5438 HGNC:5438 ENTREZ:3458 UNIPROT:P01579 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:24777831 IFN-γ induces the cytotoxic function of IL-4 DCs but not IL-15 DCs. iNOS expression was induced by IFN-gamma stimulation in IL4-DC but not in IL15DC via STAT1. PMID:21930769 IFNG/IFNGR1 signaling is required for immune rejection of tumors References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNG"/> <bbox w="86.0" h="46.0" x="4662.0" y="507.0"/> <glyph class="unit of information" id="_3eba1c01-cbe8-4077-ad9c-72bcaaa615df"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="4695.0" y="502.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s716_sa615"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 2 HUGO:JAK2 hgnc_id:HGNC:6192 HGNC:6192 ENTREZ:3717 UNIPROT:O60674 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14610620 JAK2 is a member of the Janus kinase family. JAK2 associated with IL13RA1 participates in signal transduction. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:20231889 Loss of Jak2 selectively suppresses DC-mediated innate immune response Loss of Jak2 Impairs the Activation of STAT3, 4, 5, and 6 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK2"/> <bbox w="80.0" h="40.0" x="4765.0" y="610.0"/> <glyph class="state variable" id="_e32efa37-8342-4328-93b6-f534cdc7f940"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4760.0" y="625.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s715_sa616"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="4675.0" y="610.0"/> <glyph class="state variable" id="_9f4401bc-146e-45d6-b2a7-528956f62135"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4670.0" y="625.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s714_sa617"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon gamma receptor 2 HUGO:IFNGR2 hgnc_id:HGNC:5440 HGNC:5440 ENTREZ:3460 UNIPROT:P38484 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:17683974 IFNG dimer binds to receptor contained two IFNGR1 and two IFNGR2 subunits. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNGR2"/> <bbox w="80.0" h="50.0" x="4665.0" y="555.0"/> <glyph class="unit of information" id="_ba30de94-c1da-4482-8717-12a4cace021a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4682.5" y="550.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s713_sa618"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon gamma receptor 1 HUGO:IFNGR1 hgnc_id:HGNC:5439 HGNC:5439 ENTREZ:3459 UNIPROT:P15260 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:17683974 IFNG dimer binds to receptor contained two IFNGR1 and two IFNGR2 subunits. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNGR1"/> <bbox w="80.0" h="50.0" x="4755.0" y="555.0"/> <glyph class="state variable" id="_6ad6c05d-4de3-41d4-be5e-e56919dc4c5c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4747.5" y="574.9602"/> </glyph> <glyph class="unit of information" id="_99967eb6-d04f-4ffc-afb5-2728a693e46e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4772.5" y="550.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2093_sa674" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 3 HUGO:JAK3 hgnc_id:HGNC:6193 HGNC:6193 ENTREZ:3718 UNIPROT:P52333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK3"/> <bbox w="80.0" h="40.0" x="2865.0" y="700.0"/> </glyph> <glyph class="macromolecule" id="s2097_sa636" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD209 molecule HUGO:CD209 hgnc_id:HGNC:1641 HGNC:1641 ENTREZ:30835 UNIPROT:Q9NNX6 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:25582338 DC-specific marker DC-SIGN (CD209) was expressed significantly less on IL-15 DCs compared with IL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD209"/> <bbox w="80.0" h="50.0" x="6045.0" y="2935.0"/> <glyph class="unit of information" id="_cedad9d0-aa2d-4a72-b893-75980491f0f1"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6062.5" y="2930.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1066_sa637" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon gamma HUGO:IFNG hgnc_id:HGNC:5438 HGNC:5438 ENTREZ:3458 UNIPROT:P01579 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:24777831 IFN-γ induces the cytotoxic function of IL-4 DCs but not IL-15 DCs. iNOS expression was induced by IFN-gamma stimulation in IL4-DC but not in IL15DC via STAT1. PMID:21930769 IFNG/IFNGR1 signaling is required for immune rejection of tumors References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNG"/> <bbox w="82.5" h="42.5" x="5755.0" y="2150.625"/> </glyph> <glyph class="nucleic acid feature" id="s1244_sa638" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon gamma HUGO:IFNG hgnc_id:HGNC:5438 HGNC:5438 ENTREZ:3458 UNIPROT:P01579 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:8700208, PMID:9715265, PMID:11449378 IL-12 signaling induces STAT4 tyrosine phosphorylation. And induces IFNG production via binding of Stat4 to IFNG promoter GAS element. PMID:11801649, PMID:11449378 IL 12and IL-18 synergistically enhance IFN-gamma production in human NK cells. IL-12-activated STAT4 interacts with c-Jun to form a protein-protein complex. c-Jun induced by IL-12 plus IL-18 exhibits a markedly enhanced AP-1-binding activity and induces INFG promoter. PMID:12759422 IL-18 induces NF-κB binding to the IFN-γ gene promoter and induction of gene expression. IL-15 activated the binding of STAT1, STAT3, STAT4, and STAT5 to the regulatory sites of the IFNG gene. PMID:18768831, PMID:16713975 TGF-β inhibits NK cell IFN-γ and TNF-α production following CD16 activation. TGF-β signaling could target IFNG gene expression via TBX21 (TBET) and in a SMAD-dependent fashion that is independent of T-BET. SMAD3 can directly interact with IFNG promoter. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNG"/> <bbox w="82.5" h="26.25" x="5753.75" y="2075.625"/> <glyph class="unit of information" id="_fa1e1143-fdbf-4480-84a3-c76c29bcbbf0"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5785.0" y="2070.625"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s1243_sa639" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon gamma HUGO:IFNG hgnc_id:HGNC:5438 HGNC:5438 ENTREZ:3458 UNIPROT:P01579 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 IL15 induces IFNG expression in DC via STAT3. PMID:24829413 STAT5 is phosphorylated downstream IL2, It upregulate the promoter activity of both IL2RA and IFNG in dendritic cells downstream of IL2 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNG"/> <bbox w="77.5" h="36.25" x="5756.25" y="2001.875"/> </glyph> <glyph class="macromolecule multimer" id="s2098_sa640" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon gamma HUGO:IFNG hgnc_id:HGNC:5438 HGNC:5438 ENTREZ:3458 UNIPROT:P01579 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:24777831 IFN-γ induces the cytotoxic function of IL-4 DCs but not IL-15 DCs. iNOS expression was induced by IFN-gamma stimulation in IL4-DC but not in IL15DC via STAT1. PMID:21930769 IFNG/IFNGR1 signaling is required for immune rejection of tumors References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNG"/> <bbox w="88.5" h="48.5" x="5530.75" y="2135.75"/> <glyph class="unit of information" id="_d352e975-2d58-4202-8ab8-4fe4ef25af27"> <label text="N:2"/> <bbox w="20.0" h="10.0" x="5565.0" y="2130.75"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2099_sa641" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: tumor necrosis factor HUGO:TNF hgnc_id:HGNC:11892 HGNC:11892 ENTREZ:7124 UNIPROT:P01375 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12391186 Maturation of monocyte-derived DCs was induced by TNF-α The surface levels of MHC class II increased markedly after TNF-α stimulation on CD83+ DC In contrast to the striking increase in surface expression of MHC class II, the cell surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:12928370 TNF, but not IL-1, induce monocytes to become DCs despite the presence of fibroblasts. TNF converts activated monocytes/early Mφ into DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNF"/> <bbox w="70.0" h="25.0" x="5280.0" y="1707.5"/> </glyph> <glyph class="nucleic acid feature" id="s2100_sa642" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: tumor necrosis factor HUGO:TNF hgnc_id:HGNC:11892 HGNC:11892 ENTREZ:7124 UNIPROT:P01375 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12391186 Maturation of monocyte-derived DCs was induced by TNF-α The surface levels of MHC class II increased markedly after TNF-α stimulation on CD83+ DC In contrast to the striking increase in surface expression of MHC class II, the cell surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs PMID:12928370 TNF, but not IL-1, induce monocytes to become DCs despite the presence of fibroblasts. TNF converts activated monocytes/early Mφ into DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNF"/> <bbox w="90.0" h="25.0" x="5280.0" y="1797.5"/> <glyph class="unit of information" id="_7af3b257-4a74-4794-965d-f3bb2aa43bc4"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5315.0" y="1792.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s77_sa646" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 alpha HUGO:IL1A hgnc_id:HGNC:5991 HGNC:5991 ENTREZ:3552 UNIPROT:P01583 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL1A"/> <bbox w="90.0" h="25.0" x="5661.0" y="1467.5"/> <glyph class="unit of information" id="_ddc4949c-18b8-4790-8680-1b44637abeda"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5696.0" y="1462.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s79_sa648" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 alpha HUGO:IL1A hgnc_id:HGNC:5991 HGNC:5991 ENTREZ:3552 UNIPROT:P01583 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL1A"/> <bbox w="80.0" h="40.0" x="5666.0" y="1520.0"/> </glyph> <glyph class="nucleic acid feature" id="s2101_sa649" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 HUGO:IL6 hgnc_id:HGNC:6018 HGNC:6018 ENTREZ:3569 UNIPROT:P05231 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6"/> <bbox w="70.0" h="25.0" x="1460.0" y="2467.5"/> </glyph> <glyph class="nucleic acid feature" id="s2102_sa650" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 HUGO:IL6 hgnc_id:HGNC:6018 HGNC:6018 ENTREZ:3569 UNIPROT:P05231 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6"/> <bbox w="90.0" h="25.0" x="1450.0" y="2557.5"/> <glyph class="unit of information" id="_6cbce6ce-ca96-45e1-a1d2-124401d4439d"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="1485.0" y="2552.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s741_sa651" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:16713974 TLR2 activates (induses phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages. References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 3 HUGO:MAPK3 hgnc_id:HGNC:6877 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 DSN1 homolog, MIS12 kinetochore complex component HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410 mitogen-activated protein kinase 1 HUGO:MAPK1 hgnc_id:HGNC:6871 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 6 HUGO:MAPK6 hgnc_id:HGNC:6879 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 mitogen-activated protein kinase 4 HUGO:MAPK4 hgnc_id:HGNC:6878 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 PMID:25582338 IL4 signaling activates ERK1/2 pathwway. PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ERK*"/> <bbox w="80.0" h="40.0" x="4615.0" y="1790.0"/> <glyph class="state variable" id="_766c6e9b-5102-470f-bd9a-34864e801550"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4610.0" y="1805.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s753_sa652" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase 3 HUGO:MAPK3 hgnc_id:HGNC:6877 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 DSN1 homolog, MIS12 kinetochore complex component HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410 mitogen-activated protein kinase 1 HUGO:MAPK1 hgnc_id:HGNC:6871 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 mitogen-activated protein kinase 6 HUGO:MAPK6 hgnc_id:HGNC:6879 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 mitogen-activated protein kinase 4 HUGO:MAPK4 hgnc_id:HGNC:6878 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4 PMID:25582338 IL4 signaling activates ERK1/2 pathwway. PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ERK*"/> <bbox w="80.0" h="40.0" x="4615.0" y="1870.0"/> <glyph class="state variable" id="_a31ea903-0e1d-40ba-809b-3eed4d00441d"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4607.5" y="1885.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s139_sa654" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: nitric oxide synthase 2 HUGO:NOS2 hgnc_id:HGNC:7873 HGNC:7873 ENTREZ:4843 UNIPROT:P35228 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:17476345 NOS2, a heme-containing enzyme that catalyzes the synthesis of NO and citrulline from l‐Arg, is expressed by various cells of the immune system, and its activa- tion is considered a hallmark of classically activated macrophages (also known as M1 macrophages), a macrophage subset that pro- duces proinflammatory cytokines and acts as the effector cell in the killing of invading pathogens and tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NOS2"/> <bbox w="79.5" h="23.75" x="3652.25" y="3193.125"/> <glyph class="unit of information" id="_36b4bd9a-cc4d-4a30-8df5-a45913a90922"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3682.0" y="3188.125"/> </glyph> </glyph> <glyph class="macromolecule" id="s140_sa655" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: nitric oxide synthase 2 HUGO:NOS2 hgnc_id:HGNC:7873 HGNC:7873 ENTREZ:4843 UNIPROT:P35228 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:24777831 The cytotoxic activity of IL-4 and IL-15 DCs depends on iNOS expression and NO secretion References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NOS2"/> <bbox w="73.5" h="33.75" x="3658.25" y="3263.125"/> </glyph> <glyph class="nucleic acid feature" id="s138_sa653" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: nitric oxide synthase 2 HUGO:NOS2 hgnc_id:HGNC:7873 HGNC:7873 ENTREZ:4843 UNIPROT:P35228 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:24777831 iNOS expression was induced by IFN-gamma stimulation in IL4-DC but not in IL15DC via STAT1. IL15 induces iNOS(NOS2) expression via STAT3 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NOS2"/> <bbox w="66.5" h="33.75" x="3655.25" y="3103.125"/> </glyph> <glyph class="nucleic acid feature" id="s2106_sa659" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:24777831, PMID:19811323 The expression of MHC Class I molecules (controlled by STAT-1 and IRF-1) was increased following IFN-γ treatment References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="70.0" h="25.0" x="3710.0" y="1975.0"/> </glyph> <glyph class="nucleic acid feature" id="s2107_sa660" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:24777831, PMID:19811323 The expression of MHC Class I molecules (controlled by STAT-1 and IRF-1) was increased following IFN-γ treatment References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="90.0" h="25.0" x="3700.0" y="2045.0"/> <glyph class="unit of information" id="_6a7b211f-181f-416e-98a6-e432343ac7dd"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3735.0" y="2040.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2108_sa661" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class I, A HUGO:HLA-A hgnc_id:HGNC:4931 HGNC:4931 ENTREZ:3105 UNIPROT:P01891 proline rich coiled-coil 2B HUGO:PRRC2B hgnc_id:HGNC:28121 HGNC:28121 ENTREZ:84726 UNIPROT:Q5JSZ5 protein phosphatase 1 regulatory subunit 10 HUGO:PPP1R10 hgnc_id:HGNC:9284 HGNC:9284 ENTREZ:5514 UNIPROT:Q96QC0 major histocompatibility complex, class I, E HUGO:HLA-E hgnc_id:HGNC:4962 HGNC:4962 ENTREZ:3133 UNIPROT:P13747 HLA-F antisense RNA 1 HUGO:HLA-F-AS1 hgnc_id:HGNC:26645 HGNC:26645 ENTREZ:285830 major histocompatibility complex, class I, G HUGO:HLA-G hgnc_id:HGNC:4964 HGNC:4964 ENTREZ:3135 UNIPROT:P17693 major histocompatibility complex, class I, K (pseudogene) HUGO:HLA-K hgnc_id:HGNC:4969 HGNC:4969 ENTREZ:3138 major histocompatibility complex, class I, L (pseudogene) HUGO:HLA-L hgnc_id:HGNC:4970 HGNC:4970 ENTREZ:3139 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556, PMID:10559964 MHC class I molecules is heterodimers that consist of two polypeptide chains, α and β2-microglobulin (b2m). The two chains are linked noncovalently via interaction of b2m and the α3 domain. Only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The MHC class I heavy chain, a transmembrane glycoprotein of approximately 44 kDa, binds upon synthesis to the membrane-associated endoplasmic reticulum (ER) chaperone, calnexin (CNX). Upon dissociation from CNX, the heavy chain binds β2 microglobulin (β2m) and is incorporated into the peptide-loading complex. The other constituents of the complex are the two subunits of the transporter associated with antigen processing (TAP1 and TAP2), the transmembrane glycoprotein tapasin, the soluble ER chaperone calreticulin (CRT), and the soluble thiol oxidoreductase ERp57. Peptides are transported into the ER from the cytosol via TAP, and, if necessary, they are trimmed by an ER-associated aminopeptidase (ERAAP or ERAP1) to 8–10 amino acids, the length that is generally required for association with class I molecules. If the peptide has the appropriate sequence, it binds to the MHC class I-β2m heterodimer, which is released from the peptide-loading complex. The fully assembled class I molecule then leaves the ER and travels via the Golgi apparatus to the plasma membrane, where it is accessible to CD8+ T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class I*"/> <bbox w="80.0" h="45.0" x="3705.0" y="2097.5"/> <glyph class="state variable" id="_2014049c-ceed-45b5-bd6c-f94665f48de0"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3700.0" y="2115.0"/> </glyph> <glyph class="unit of information" id="_4a01c90b-9f26-46f4-9301-a27bffc7219b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3722.5" y="2092.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2109_sa662" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 1 HUGO:STAT1 hgnc_id:HGNC:11362 HGNC:11362 ENTREZ:6772 UNIPROT:P42224 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:24777831, PMID:16056253 PIAS1 is a a transcriptional repressor of STAT1. PIAS1 expression was not detected in DCs generated with IL-4. In contrast, the basal level of PIAS1 expression was substantially elevated in IL-15 DCs. combination of PIAS1 with STAT-3 inhibition led to a partial restoration of iNOS expression, NO production, and DC tumoricidal function References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT1"/> <bbox w="70.0" h="25.0" x="4590.0" y="737.5"/> </glyph> <glyph class="nucleic acid feature" id="s2110_sa663" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 1 HUGO:STAT1 hgnc_id:HGNC:11362 HGNC:11362 ENTREZ:6772 UNIPROT:P42224 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:24777831, PMID:16056253 PIAS1 is a a transcriptional repressor of STAT1. PIAS1 expression was not detected in DCs generated with IL-4. In contrast, the basal level of PIAS1 expression was substantially elevated in IL-15 DCs. combination of PIAS1 with STAT-3 inhibition led to a partial restoration of iNOS expression, NO production, and DC tumoricidal function References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT1"/> <bbox w="90.0" h="25.0" x="4580.0" y="817.5"/> <glyph class="unit of information" id="_1fe4ccf4-87ee-48ca-ba94-16d51ee2a27e"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="4615.0" y="812.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2111_sa664" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: protein inhibitor of activated STAT 1 HUGO:PIAS1 hgnc_id:HGNC:2752 HGNC:2752 ENTREZ:8554 UNIPROT:O75925 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24777831, PMID:16056253 PIAS1 is a a transcriptional repressor of STAT1. PIAS1 expression was not detected in DCs generated with IL-4. In contrast, the basal level of PIAS1 expression was substantially elevated in IL-15 DCs. combination of PIAS1 with STAT-3 inhibition led to a partial restoration of iNOS expression, NO production, and DC tumoricidal function References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PIAS1"/> <bbox w="80.0" h="40.0" x="4715.0" y="780.0"/> </glyph> <glyph class="macromolecule" id="s2112_sa665" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD8a molecule HUGO:CD8A hgnc_id:HGNC:1706 HGNC:1706 ENTREZ:925 UNIPROT:P01732 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:21930769 PMID:21930765 CD8a is a marker of DC supset which activates T cells References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD8A"/> <bbox w="80.0" h="50.0" x="6040.0" y="3142.5"/> <glyph class="unit of information" id="_4d8a2c78-7ce9-43c5-befb-58e92e8b15a4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6057.5" y="3137.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2113_sa666" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 2 HUGO:SOCS2 hgnc_id:HGNC:19382 HGNC:19382 ENTREZ:8835 UNIPROT:O14508 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). SOCS proteins are characterized by the presence of an Src homology 2 domain and a C-terminal conserved domain called the SOCS box, and their inhibitory effects derive from direct interaction with cytokine receptors and/or Janus kinases (JAKs), thereby preventing recruitment of STATs to the signaling complex References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS2"/> <bbox w="80.0" h="40.0" x="4875.0" y="1680.0"/> </glyph> <glyph class="macromolecule" id="s2114_sa667" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 1 HUGO:SOCS1 hgnc_id:HGNC:19383 HGNC:19383 ENTREZ:8651 UNIPROT:O15524 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). SOCS1 expression is also STAT1 dependent. SOCS proteins are characterized by the presence of an Src homology 2 domain and a C-terminal conserved domain called the SOCS box, and their inhibitory effects derive from direct interaction with cytokine receptors and/or Janus kinases (JAKs), thereby preventing recruitment of STATs to the signaling complex References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS1"/> <bbox w="80.0" h="40.0" x="4965.0" y="1680.0"/> </glyph> <glyph class="nucleic acid feature" id="s2115_sa668" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 2 HUGO:SOCS2 hgnc_id:HGNC:19382 HGNC:19382 ENTREZ:8835 UNIPROT:O14508 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS2"/> <bbox w="70.0" h="25.0" x="4880.0" y="1527.5"/> </glyph> <glyph class="nucleic acid feature" id="s2116_sa669" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 3 HUGO:SOCS3 hgnc_id:HGNC:19391 HGNC:19391 ENTREZ:9021 UNIPROT:O14543 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS3"/> <bbox w="70.0" h="25.0" x="4780.0" y="1527.5"/> </glyph> <glyph class="nucleic acid feature" id="s2117_sa670" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 1 HUGO:SOCS1 hgnc_id:HGNC:19383 HGNC:19383 ENTREZ:8651 UNIPROT:O15524 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). SOCS1 expression is also STAT1 dependent. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS1"/> <bbox w="70.0" h="25.0" x="4970.0" y="1527.5"/> </glyph> <glyph class="nucleic acid feature" id="s2118_sa671" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 2 HUGO:SOCS2 hgnc_id:HGNC:19382 HGNC:19382 ENTREZ:8835 UNIPROT:O14508 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS2"/> <bbox w="90.0" h="25.0" x="4870.0" y="1597.5"/> <glyph class="unit of information" id="_6d1fb3d3-afe4-4e69-98e2-5efdfaf86bfb"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="4905.0" y="1592.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2119_sa672" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 3 HUGO:SOCS3 hgnc_id:HGNC:19391 HGNC:19391 ENTREZ:9021 UNIPROT:O14543 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS3"/> <bbox w="90.0" h="25.0" x="4770.0" y="1597.5"/> <glyph class="unit of information" id="_d39e32b6-7aeb-4e1d-9d37-f8827b3217da"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="4805.0" y="1592.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2120_sa673" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: suppressor of cytokine signaling 1 HUGO:SOCS1 hgnc_id:HGNC:19383 HGNC:19383 ENTREZ:8651 UNIPROT:O15524 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14764699 SOCS1 and SOCS3 are upregulated in mature DC. SOCS2 in immature DC. SOCS1 and SOCS2 expression is induced by IL4 signaling, and SOCS3 expression is upregulated more by GM-CSF (CSF2). SOCS1 expression is also STAT1 dependent. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SOCS1"/> <bbox w="90.0" h="25.0" x="4960.0" y="1597.5"/> <glyph class="unit of information" id="_6914823b-8700-4fb4-b105-b4a6e7c93c83"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="4995.0" y="1592.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2123_sa676" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: class II major histocompatibility complex transactivator HUGO:CIITA hgnc_id:HGNC:7067 HGNC:7067 ENTREZ:4261 UNIPROT:P33076 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:8624807 CIITA is required for both constitutive and IFNγ-inducible expression of MHC class II genes CIITA-deficient (−/−) mice do not express conventional MHC class II molecules on the surface of splenic B cells and dendritic cells. PMID:11514596 Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (Ciita) Expression and down regulation of MHCII expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CIITA"/> <bbox w="80.0" h="40.0" x="3485.0" y="1960.0"/> </glyph> <glyph class="macromolecule" id="s2124_sa677" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="3585.0" y="2080.0"/> <glyph class="state variable" id="_84ce1657-2654-4183-abcf-91886e53da41"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3580.0" y="2095.0"/> </glyph> <glyph class="unit of information" id="_fc9fe2da-0e1d-48d7-ba09-16a5d5d3a9a2"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3602.5" y="2075.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2125_sa678" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="70.0" h="25.0" x="3590.0" y="1967.5"/> </glyph> <glyph class="nucleic acid feature" id="s2126_sa679" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="90.0" h="25.0" x="3580.0" y="2027.5"/> <glyph class="unit of information" id="_b2a0c4dc-f8b9-49ec-b2ae-e894d573a7f1"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3615.0" y="2022.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2127_sa680" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: class II major histocompatibility complex transactivator HUGO:CIITA hgnc_id:HGNC:7067 HGNC:7067 ENTREZ:4261 UNIPROT:P33076 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. PMID:11514596 Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (Ciita) Expression and down regulation of MHCII expression. ERK and p38 MAPK suppress CIITA expression by decreasing histone acetylation PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CIITA"/> <bbox w="70.0" h="25.0" x="3490.0" y="1857.5"/> </glyph> <glyph class="nucleic acid feature" id="s2128_sa681" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: class II major histocompatibility complex transactivator HUGO:CIITA hgnc_id:HGNC:7067 HGNC:7067 ENTREZ:4261 UNIPROT:P33076 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages. PMID:11514596 Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (Ciita) Expression and down regulation of MHCII expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CIITA"/> <bbox w="90.0" h="25.0" x="3480.0" y="1907.5"/> <glyph class="unit of information" id="_6f156052-c71b-4150-a7f5-76341d618391"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3515.0" y="1902.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2133_sa686" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon regulatory factor 4 HUGO:IRF4 hgnc_id:HGNC:6119 HGNC:6119 ENTREZ:3662 UNIPROT:Q15306 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:24362890 IRF4 as a regulatory determinant of enhanced formation of peptide–MHC class II in CD11b+ DCs. PMID:24076050 IRF4 plays a role in DCs where it controls the initiation of Th2 cell responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRF4"/> <bbox w="80.0" h="40.0" x="3625.0" y="2970.0"/> </glyph> <glyph class="nucleic acid feature" id="s2135_sa689" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibitor of DNA binding 3, HLH protein HUGO:ID3 hgnc_id:HGNC:5362 HGNC:5362 ENTREZ:3399 UNIPROT:Q02535 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:21191065 Cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. LGALS1 upregulates ID3 expression, then ID3 upregulates expression of IL10 in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ID3"/> <bbox w="70.0" h="25.0" x="1310.0" y="1648.75"/> </glyph> <glyph class="nucleic acid feature" id="s2136_sa690" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibitor of DNA binding 3, HLH protein HUGO:ID3 hgnc_id:HGNC:5362 HGNC:5362 ENTREZ:3399 UNIPROT:Q02535 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:21191065 Cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. LGALS1 upregulates ID3 expression, then ID3 upregulates expression of IL10 in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ID3"/> <bbox w="90.0" h="25.0" x="1300.0" y="1598.75"/> <glyph class="unit of information" id="_20d5fe75-2ab1-4713-b3c1-4a6f57ced152"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="1335.0" y="1593.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s2137_sa691" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inhibitor of DNA binding 3, HLH protein HUGO:ID3 hgnc_id:HGNC:5362 HGNC:5362 ENTREZ:3399 UNIPROT:Q02535 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:21191065 Cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. LGALS1 upregulates ID3 expression, then ID3 upregulates expression of IL10 in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ID3"/> <bbox w="80.0" h="40.0" x="1305.0" y="1531.25"/> </glyph> <glyph class="macromolecule" id="s2140_sa693"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: galectin 1 HUGO:LGALS1 hgnc_id:HGNC:6561 HGNC:6561 ENTREZ:3956 UNIPROT:P09382 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:21191065 Cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. LGALS1 upregulates ID3 expression, then ID3 upregulates expression of IL10 in DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LGALS1"/> <bbox w="80.0" h="40.0" x="2230.0" y="4095.0"/> </glyph> <glyph class="nucleic acid feature" id="s2141_sa694" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 3 HUGO:STAT3 hgnc_id:HGNC:11364 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT3"/> <bbox w="90.0" h="25.0" x="1190.0" y="2007.5"/> <glyph class="unit of information" id="_405beee0-7845-410b-a363-91bd6d8cbab5"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="1225.0" y="2002.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2142_sa695" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 3 HUGO:STAT3 hgnc_id:HGNC:11364 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT3"/> <bbox w="70.0" h="25.0" x="1200.0" y="2077.5"/> </glyph> <glyph class="nucleic acid feature" id="s2143_sa696" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="70.0" h="25.0" x="1090.0" y="2077.5"/> </glyph> <glyph class="nucleic acid feature" id="s2144_sa697" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:23383203 Il10 signaling not only activates JAK1/STAT3 signaling in DC but also upregulates protein level of key elements IL10, JAK1 and STAT3 and provides positive feedback. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="90.0" h="25.0" x="1080.0" y="1987.5"/> <glyph class="unit of information" id="_abf55d8f-c424-470e-8f6d-d16b641449d9"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="1115.0" y="1982.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2146_sa702" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF receptor associated factor 3 HUGO:TRAF3 hgnc_id:HGNC:12033 HGNC:12033 ENTREZ:7187 UNIPROT:Q13114 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16306937 IL10 and IFNB expression is TRAF3 dependent on mRNA level downstream of TLR4 signaling.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAF3"/> <clone/> <bbox w="80.0" h="40.0" x="5625.0" y="1180.0"/> </glyph> <glyph class="macromolecule" id="s2146_sa704" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF receptor associated factor 3 HUGO:TRAF3 hgnc_id:HGNC:12033 HGNC:12033 ENTREZ:7187 UNIPROT:Q13114 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16306937 IL10 and IFNB expression is TRAF3 dependent on mRNA level downstream of TLR4 signaling.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAF3"/> <clone/> <bbox w="80.0" h="40.0" x="5625.0" y="1260.0"/> </glyph> <glyph class="complex" id="s2147_csa109" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:TICAM1:TLR4 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:20154735 ,PMID:16306937 TICAM1 (TRIF)/TRAF pathway downstream of TLR4 is MYD88 independent. PMID:17114424 Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2147"/> <bbox w="120.0" h="190.0" x="6225.0" y="975.0"/> <glyph class="macromolecule" id="s2148_sa700"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: toll like receptor 4 HUGO:TLR4 hgnc_id:HGNC:11850 HGNC:11850 ENTREZ:7099 UNIPROT:O00206 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. PMID:16489357, PMID:17704786, PMID:23811849 TLR4 signaling induces antigens for presentation, by DC in tumors. syngeneic WT, Trif-/-, Tlr1-/-, Tlr2-/-, Tlr3-/-, Tlr5-/-, Tlr6-/-, Tlr7-/- or Tlr9-/- DCs could present antigen from dying tumor cells, Tlr4-/- and Myd88-/- DCs were defective in this function PMID:16785500 ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages downstream of TLR4 MyD88-dependent signaling. PMID:11477091,PMID:14607893 Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10, which is also associated to Th1 responses. In contrast, TLR2 stimulation failed to induce IL-12 p70 and interferon-gamma inducible protein (IP)-10 but resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development. TLR2 stimulation also resulted in preferential induction of IL-8 and p19/IL-23. Thus, Escherichia coli LPS and flagellin, which trigger TLR4 and TLR5, respectively, instruct DCs to stimulate Th1 responses via IL-12p70 production, which depends on the phosphorylation of p38 and c-Jun N-terminal kinase 1/2. In contrast, the TLR2 agonist, Pam3cys, and the Th2 stimulus, schistosome egg Ags: 1) barely induce IL-12p70; 2) stimulate sustained duration and magnitude of extracellular signal-regulated kinase 1/2 phosphorylation, which results in stabilization of the transcription factor c-Fos, a suppressor of IL-12; and 3) yield a Th2 bias. Thus, distinct TLR agonists differentially modulate extracellular signal-regulated kinase signaling, c-Fos activity, and cytokine responses in DCs to stimulate different Th responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TLR4"/> <bbox w="80.0" h="50.0" x="6245.0" y="1025.0"/> <glyph class="unit of information" id="_9580ca56-e78e-407e-9c7d-9c13d2392fc3"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6262.5" y="1020.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2151_sa703"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: toll like receptor adaptor molecule 1 HUGO:TICAM1 hgnc_id:HGNC:18348 HGNC:18348 ENTREZ:148022 UNIPROT:Q8IUC6 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:16917499 TIKAM1(TRIF) is an adaptor of TLR signaling, TLR signaling via ARHGEF2 (GEFH1)and RHOB regulates MHCII surface expression PMID:20154735 ,PMID:16306937 TICAM1 (TRIF)/TRAF pathway downstream of TLR4 is MYD88 independent. PMID:17114424 Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TICAM1"/> <bbox w="80.0" h="40.0" x="6245.0" y="1085.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2152_sa698" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: toll like receptor adaptor molecule 1 HUGO:TICAM1 hgnc_id:HGNC:18348 HGNC:18348 ENTREZ:148022 UNIPROT:Q8IUC6 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:16917499 TIKAM1(TRIF) is an adaptor of TLR signaling, TLR signaling via ARHGEF2 (GEFH1)and RHOB regulates MHCII surface expression PMID:20154735 ,PMID:16306937 TICAM1 (TRIF)/TRAF pathway downstream of TLR4 is MYD88 independent. PMID:17114424 Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TICAM1"/> <bbox w="80.0" h="40.0" x="5925.0" y="740.0"/> </glyph> <glyph class="macromolecule" id="s742_sa706" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:16713974 TLR2 activates (induses phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages. References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: HUGO:MAPK8 HUGO:MAPK9 HUGO:MAPK10 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16713974 TLR2 activates (induces phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages. This activation is inhibited by IFNG signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JNK*"/> <bbox w="80.0" h="40.0" x="4791.125" y="1798.25"/> <glyph class="state variable" id="_d9c2a87b-d763-41bd-bf0f-c7fac16aacd3"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4786.125" y="1813.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s752_sa707" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: HUGO:MAPK8 HUGO:MAPK9 HUGO:MAPK10 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16713974 TLR2 activates (induces phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages. This activation is inhibited by IFNG signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JNK*"/> <bbox w="80.0" h="40.0" x="4795.0" y="1870.0"/> <glyph class="state variable" id="_ff5bbbc1-379a-4959-82c7-6c158ac5becd"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="4787.5" y="1885.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s326_sa708" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Fos proto-oncogene, AP-1 transcription factor subunit HUGO:FOS hgnc_id:HGNC:3796 HGNC:3796 ENTREZ:2353 UNIPROT:P01100 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:21385848, PMID:22634314 c-Fos downregulates mRNA expression of TNF, IL6, IL1B, IL12p40. IL12p35, IL23a Additionally Fos downregulates CD86, CD40 surface expression, IL2 secretion and Tcell activation. PMID:22634314 Expression of IL-10 was enhanced in DC overexpressed Fos. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FOS"/> <clone/> <bbox w="80.0" h="40.0" x="4955.0" y="1930.0"/> </glyph> <glyph class="macromolecule" id="s326_sa709" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Fos proto-oncogene, AP-1 transcription factor subunit HUGO:FOS hgnc_id:HGNC:3796 HGNC:3796 ENTREZ:2353 UNIPROT:P01100 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:21385848, PMID:22634314 c-Fos downregulates mRNA expression of TNF, IL6, IL1B, IL12p40. IL12p35, IL23a Additionally Fos downregulates CD86, CD40 surface expression, IL2 secretion and Tcell activation. PMID:22634314 Expression of IL-10 was enhanced in DC overexpressed Fos. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FOS"/> <clone/> <bbox w="80.0" h="40.0" x="4955.0" y="2090.0"/> </glyph> <glyph class="nucleic acid feature" id="s767_sa710" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Fos proto-oncogene, AP-1 transcription factor subunit HUGO:FOS hgnc_id:HGNC:3796 HGNC:3796 ENTREZ:2353 UNIPROT:P01100 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16713974 INFG signaling ingibits FOS expression References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FOS"/> <bbox w="70.0" h="25.0" x="4960.0" y="1797.5"/> </glyph> <glyph class="nucleic acid feature" id="s768_sa711" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Fos proto-oncogene, AP-1 transcription factor subunit HUGO:FOS hgnc_id:HGNC:3796 HGNC:3796 ENTREZ:2353 UNIPROT:P01100 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:21385848 c-Fos has binding sites for mir155, Fos mRNA was reduced in DC2114 cells overexpressing miR155. cFos is inhibited during the DC maturations. c-Fos–transduced DC2114 cells retained the ability to up-regulate the expression of proinflammatory cytokine mRNAs during maturation, this induction tended to be reduced 2- to 3-fold relative to untransduced DC2114 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FOS"/> <bbox w="90.0" h="25.0" x="4950.0" y="1847.5"/> <glyph class="unit of information" id="_da1244f3-80a1-4760-bc63-e456dd76ea49"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="4985.0" y="1842.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2154_sa712" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: microRNA 155 HUGO:MIR155 hgnc_id:HGNC:31542 HGNC:31542 ENTREZ:406947 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:21385848 miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. miR155 expression was increased strongly in mature Mo-DCs relative to monocytes and immature Mo-DCs. miR155 accumulation was induced rapidly and increased progressively, reaching maximal levels after 24-48 hours of stimulation with LPS (TLR4 signaling) and IFNα. c-Fos has binding sites for mir155, Fos mRNA was reduced in DC2114 cells overexpressing miR155. cFos is inhibited during the DC maturations. PMID:19193853 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MIR155"/> <bbox w="90.0" h="25.0" x="5041.0" y="1787.5"/> <glyph class="unit of information" id="_0833aba4-5ae0-4b4a-a9b0-d533115454cc"> <label text="asRNA"/> <bbox w="30.0" h="10.0" x="5071.0" y="1782.5"/> </glyph> </glyph> <glyph class="complex" id="s2155_csa110" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:FOS:MIR155 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:21385848 miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2155"/> <bbox w="110.0" h="90.0" x="5055.0" y="1880.0"/> <glyph class="nucleic acid feature" id="s2157_sa713"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: microRNA 155 HUGO:MIR155 hgnc_id:HGNC:31542 HGNC:31542 ENTREZ:406947 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:21385848 miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. miR155 expression was increased strongly in mature Mo-DCs relative to monocytes and immature Mo-DCs. miR155 accumulation was induced rapidly and increased progressively, reaching maximal levels after 24-48 hours of stimulation with LPS (TLR4 signaling) and IFNα. c-Fos has binding sites for mir155, Fos mRNA was reduced in DC2114 cells overexpressing miR155. cFos is inhibited during the DC maturations. PMID:19193853 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MIR155"/> <bbox w="90.0" h="25.0" x="5060.0" y="1917.5"/> <glyph class="unit of information" id="_cfcbdd02-38e4-46e4-a6de-c37239ff273d"> <label text="asRNA"/> <bbox w="30.0" h="10.0" x="5090.0" y="1912.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2156_sa714"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Fos proto-oncogene, AP-1 transcription factor subunit HUGO:FOS hgnc_id:HGNC:3796 HGNC:3796 ENTREZ:2353 UNIPROT:P01100 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:21385848 c-Fos has binding sites for mir155, Fos mRNA was reduced in DC2114 cells overexpressing miR155. cFos is inhibited during the DC maturations. c-Fos–transduced DC2114 cells retained the ability to up-regulate the expression of proinflammatory cytokine mRNAs during maturation, this induction tended to be reduced 2- to 3-fold relative to untransduced DC2114 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FOS"/> <bbox w="90.0" h="25.0" x="5060.0" y="1887.5"/> <glyph class="unit of information" id="_94f88f28-5a14-4980-8780-902642b77179"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5095.0" y="1882.5"/> </glyph> </glyph> </glyph> <glyph class="source and sink" id="s2158_sa715" compartmentRef="c2_ca2"> <label text="csa110_degraded"/> <bbox w="30.0" h="30.0" x="5230.0" y="1935.0"/> </glyph> <glyph class="macromolecule" id="s2160_sa508" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD40 molecule HUGO:CD40 hgnc_id:HGNC:11919 HGNC:11919 ENTREZ:958 UNIPROT:P25942 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:11964292, PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:8760829 Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD40"/> <bbox w="80.0" h="40.0" x="5000.0" y="3150.0"/> <glyph class="unit of information" id="_7fd569f5-5a7b-4df5-ac6a-cee472d779c6"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5017.5" y="3145.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2161_sa717" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X-C motif chemokine ligand 10 HUGO:CXCL10 hgnc_id:HGNC:10637 HGNC:10637 ENTREZ:3627 UNIPROT:P02778 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:11477091 TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-γ inducible protein (IP)-10 (CXCL10), which is also associated to Th1 responses References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCL10"/> <bbox w="80.0" h="40.0" x="5675.0" y="1880.0"/> </glyph> <glyph class="macromolecule" id="s2162_sa718" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:12594251 Dendritic cells can capture the antigens through the ‘nibbling’ of live tumour cells, Class A Scavenger Receptor (MSR1) regulates the process. Internalized membrane colocalized with SR ligand and entered the endosomal pathway. DC very efficiently acquired and internalized gp100 tumor Ag expressed at the surface of viable adenocarcinoma cells via recombinant adenoviral infection. Cross-presentation of gp100 by DC to MHC class I-restricted T cells was inhibited by polyanionic SR ligand and an Ab to type A SR (SR-A), whereas Ab to the class B SR CD36, which mediates uptake of apoptotic cells, induced no inhibition. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MCR1"/> <bbox w="80.0" h="50.0" x="3160.0" y="3395.0"/> <glyph class="unit of information" id="_b2d62544-9d8c-4b70-94e4-6e2475425ece"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3177.5" y="3390.0"/> </glyph> </glyph> <glyph class="phenotype" id="s2164_sa720"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22437871 There are currently four sets of molecules that are known to be released by apoptotic cells that function as 'find me' signals: lipid lysophosphatidylcholine (LPC), sphingosine 1-phosphate (S1P), CX3CL1 (also known as fractalkine), and the nucleotides ATP and UTP References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FIND ME"/> <bbox w="210.0" h="95.0" x="2405.0" y="4087.5"/> </glyph> <glyph class="phenotype" id="s2165_sa721"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22437871 The eat me signals are membrane-bound and serve as markers for phagocytes for recognizing and internalizing dying cells. These signals include phosphatidylserine, alterations in cell-surface charge, αvβ5 integrin and CD36. The eat me signals also include molecules such as milk fat globule-EGF factor 8 (MFG-E8; also known as lactadherin), which bridge the phosphatidylserine of apoptotic cells with the integrin αvβ3 of DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="EAT ME"/> <bbox w="222.5" h="98.75" x="3328.75" y="4135.625"/> </glyph> <glyph class="simple chemical" id="s2167_sa723"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:12809603 LPC is secreted by apoptotic cells PMID:12165488 Mature dendritic cell generation promoted by lysophosphatidylcholine. LPC acts through G protein-coupled receptors on differentiating monocytes to generate mature dendritic cells with the ability to stimulate IL-2 and IFN-γ production by allogeneic T lymphocytes. LPC stimulates CD86 surface expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Lysophosphatidylcholine"/> <bbox w="165.0" h="32.5" x="2527.5" y="3948.75"/> </glyph> <glyph class="simple chemical" id="s2168_sa724"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:18362204 Apoptotic cells may up-regulate SphK1 to produce and secrete S1P that serves as a "come-and-get-me" signal for scavenger cells PMID:11919175 Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. Immature and mature DC express the mRNA for different S1P receptors, such as endothelial differentiation gene (EDG)-1, EDG-3, EDG-5, and EDG-6. In immature DC, S1P stimulated pertussis toxin-sensitive Ca2+ increase actin polymerization and chemotaxis. These responses were lost by DC matured with lipopolysaccharide. In maturing DC, however, S1P inhibited the secretion of tumor necrosis factor α and interleukin (IL)-12, whereas it enhanced secretion of IL-10. As a consequence, mature DC exposed to S1P showed a reduced and increased capacity to generate allogeneic Th1 and Th2 responses, respectively. In summary, our study implicates that S1P might regulate the trafficking of DC and ultimately favor Th2 lymphocyte-dominated immunity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Sphingosine 1-phosphate"/> <bbox w="175.0" h="32.5" x="2272.5" y="4008.75"/> </glyph> <glyph class="macromolecule" id="s2169_sa725"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X3-C motif chemokine ligand 1 HUGO:CX3CL1 hgnc_id:HGNC:10647 HGNC:10647 ENTREZ:6376 UNIPROT:P78423 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:18799722 CX3CL1/fractalkine is released from dying cells PMID:18363071 Fractalkine (CX3CL1) is the only CX3C chemokine that can chemoattract natural killer (NK) cells, CD8+ T cells, monocytes, and dendritic cells. PMID:12455035 CX3CL1 induces chemoattraction and activation of DC via CX3CR1 and induces Tcell activation. Adherence of DC to cells expressed CX3CL1 resulted in phenotypic maturation and upregulated IL-12 secretion of DC, and more strong stimulation of allogeneic T-cell proliferation by DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CX3CL1"/> <bbox w="80.0" h="40.0" x="2380.0" y="3885.0"/> </glyph> <glyph class="simple chemical" id="s2170_sa726"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ATP"/> <bbox w="70.0" h="25.0" x="2485.0" y="3872.5"/> </glyph> <glyph class="simple chemical" id="s2171_sa727"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="UTP"/> <bbox w="70.0" h="25.0" x="2605.0" y="4032.5"/> </glyph> <glyph class="macromolecule" id="s2172_sa728"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: milk fat globule-EGF factor 8 protein HUGO:MFGE8 hgnc_id:HGNC:7036 HGNC:7036 ENTREZ:4240 UNIPROT:Q08431 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:22035837, PMID:15031725 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes PMID:14697347, PMID: 11146654 The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells by DCs.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MFGE8"/> <bbox w="80.0" h="40.0" x="3055.0" y="3950.0"/> </glyph> <glyph class="macromolecule" id="s2173_sa729"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD47 molecule HUGO:CD47 hgnc_id:HGNC:1682 HGNC:1682 ENTREZ:961 UNIPROT:Q08722 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11509594 CD47 binds SIRP-α on DC. SIRP-α engagement down-regulates DC function CD47-Fc potently suppressed IL-12 and TNF-α release by monocyte-derived DC stimulated by SAC. The inhibitory effect was dose dependent, and significant suppression was seen with as little as 10 ng/ml CD47-Fc (Fig. 5⇓B). Other cytokines, including IL-6 and IL-10, were also suppressed, CD47-Fc not only suppressed cytokine release by maturing DC, but also largely prevented DC phenotypic maturation. As indicated in Fig. 6⇓, CD83 and CD86 up-regulation were strongly reduced regardless of the stimulus used. For CD80, the inhibition was almost complete in response to CD40 signaling, moderate in response to SAC, and modest, but significant in response to LPS. CD40 expression was weakly up-regulated during DC maturation. In all three conditions, SIRP-α ligation by CD47-Fc abrogated the CD40 increase. Note only a slight reduction in HLA-DR expression. All together, these results demonstrate that engagement of SIRP-α largely inhibits DC maturation. PMID:10657674, PMID:10657674 CD47 is expresed on dendritic cells PMID:10657674, PMID:14568985 CD47 engagement by Thrombospondin-1 inhibits cytokine production and maturation of human dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD47"/> <bbox w="80.0" h="50.0" x="1915.0" y="3725.0"/> <glyph class="unit of information" id="_28670c43-1817-4d08-ae24-7e30e222eced"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1932.5" y="3720.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2174_sa730"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: lactotransferrin HUGO:LTF hgnc_id:HGNC:6720 HGNC:6720 ENTREZ:4057 UNIPROT:P02788 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:18364398 Talactoferrin (TLF), a recombinant human LF, is in clinical development as an anticancer agent and is entering Phase III clinical trials. Here, we show that TLF induces the maturation of human dendritic cells (DCs) derived from monocytes. TLF, at physiologically relevant concentrations (100 μg/ml) up-regulates the expression of human leukocyte antigen (HLA) class II, CD83, CD80, and CD86 costimulatory molecule and CXCR4 and CCR7 chemokine receptors, acting primarily through the p38 MAPK signaling pathway. DCs matured by TLF displayed an enhanced release of IL-8 and CXCL10, as well as a significantly reduced production of IL-6, IL-10, and CCL20. They also display a reduced ability to take up antigen and increased capacity to trigger proliferation and release IFN-γ in the presence of allogeneic human T cells. PMID:18453607 Addition of TLF to human peripheral blood or monocyte-derived dendritic cell cultures resulted in cell maturation, as evidenced by up-regulated expression of CD80, CD83, and CD86, production of proinflammatory cytokines, and increased capacity to stimulate the proliferation of allogeneic lymphocytes. PMID:24088817 Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll-like receptors 2 and 4 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LTF"/> <bbox w="80.0" h="40.0" x="5675.0" y="420.0"/> </glyph> <glyph class="macromolecule" id="s2175_sa731" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: purinergic receptor P2X 7 HUGO:P2RX7 hgnc_id:HGNC:8537 HGNC:8537 ENTREZ:5027 UNIPROT:Q99572 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="P2RX7"/> <bbox w="80.0" h="50.0" x="2425.0" y="3595.0"/> <glyph class="unit of information" id="_4e1f310e-3819-4cd9-afc2-6292e0b11995"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2442.5" y="3590.0"/> </glyph> </glyph> <glyph class="complex" id="s2176_csa111" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ATP:P2RX7 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2176"/> <bbox w="100.0" h="120.0" x="2535.0" y="3490.0"/> <glyph class="macromolecule" id="s2177_sa732"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: purinergic receptor P2X 7 HUGO:P2RX7 hgnc_id:HGNC:8537 HGNC:8537 ENTREZ:5027 UNIPROT:Q99572 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="P2RX7"/> <bbox w="80.0" h="50.0" x="2545.0" y="3535.0"/> <glyph class="unit of information" id="_b8f94f9f-b038-4a97-87d4-25a138df7fa5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2562.5" y="3530.0"/> </glyph> </glyph> <glyph class="simple chemical" id="s2178_sa733"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. </body> </html> </notes> <label text="ATP"/> <bbox w="70.0" h="25.0" x="2550.0" y="3507.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s1142_sa734" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 beta HUGO:IL1B hgnc_id:HGNC:5992 HGNC:5992 ENTREZ:3553 UNIPROT:P01584 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19767732 the TLR4 ligand HMGB1 and ATP, which are both released by tumor cells exposed to cytotoxic agents, act in concert to promote IL-1β secretion by DC ex vivo. The treatment of DC with oxidized ATP or anti-HMGB1-neutralizing antibodies prior to loading with dying tumor cells completely abolished IL-1β secretion. PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="trIL1B"/> <bbox w="80.0" h="40.0" x="5565.0" y="2220.0"/> <glyph class="unit of information" id="_8eb75146-9c3c-4342-a052-519b89c88670"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="5580.0" y="2215.0"/> </glyph> </glyph> <glyph class="complex" id="s1367_csa113" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:Caspase1*:NLRP3:PYCARD Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:19767732 the TLR4 ligand HMGB1 and ATP, which are both released by tumor cells exposed to cytotoxic agents, act in concert to promote IL-1β secretion by DC ex vivo. The treatment of DC with oxidized ATP or anti-HMGB1-neutralizing antibodies prior to loading with dying tumor cells completely abolished IL-1β secretion. PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Inflammasome"/> <bbox w="110.0" h="150.0" x="5930.0" y="2345.0"/> <glyph class="macromolecule" id="s1363_sa741"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: NLR family pyrin domain containing 3 HUGO:NLRP3 hgnc_id:HGNC:16400 HGNC:16400 ENTREZ:114548 UNIPROT:Q96P20 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19104081 Inflammasome is needfull for processing and release of IL-1beta in monocytes downstream of TLR2 or TLR4 signaling. It contains CASP1, Pycard, NLRP3 (NALP3) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NLRP3"/> <bbox w="80.0" h="40.0" x="5940.0" y="2435.0"/> </glyph> <glyph class="macromolecule" id="s1365_sa742"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: PYD and CARD domain containing HUGO:PYCARD hgnc_id:HGNC:16608 HGNC:16608 ENTREZ:29108 UNIPROT:Q9ULZ3 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19104081 Inflammasome is needfull for processing and release of IL-1beta in monocytes downstream of TLR2 or TLR4 signaling. It contains CASP1, Pycard, NLRP3 (NALP3) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PYCARD"/> <bbox w="80.0" h="40.0" x="5940.0" y="2395.0"/> </glyph> <glyph class="macromolecule" id="s1364_sa743"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: caspase 1 HUGO:CASP1 hgnc_id:HGNC:1499 HGNC:1499 ENTREZ:834 UNIPROT:P29466 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19104081 Inflammasome is needfull for processing and release of IL-1beta in monocytes downstream of TLR2 or TLR4 signaling. It contains CASP1, Pycard, NLRP3 (NALP3).After 2 hours of incubation, monocytes display clear activation of caspase-1 regardless of LPS stimulation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Caspase1*"/> <bbox w="80.0" h="40.0" x="5940.0" y="2355.0"/> </glyph> </glyph> <glyph class="complex" id="s1368_csa112" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:NLRP3:PYCARD:cleaved Caspase1* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:19767732 the TLR4 ligand HMGB1 and ATP, which are both released by tumor cells exposed to cytotoxic agents, act in concert to promote IL-1β secretion by DC ex vivo. The treatment of DC with oxidized ATP or anti-HMGB1-neutralizing antibodies prior to loading with dying tumor cells completely abolished IL-1β secretion. PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Inflammasome"/> <bbox w="110.0" h="150.0" x="5750.0" y="2345.0"/> <glyph class="macromolecule" id="s1366_sa740"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: caspase 1 HUGO:CASP1 hgnc_id:HGNC:1499 HGNC:1499 ENTREZ:834 UNIPROT:P29466 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19104081 Inflammasome is needfull for processing and release of IL-1beta downstream of TLR2 or TLR4 signaling. It contains CASP1, Pycard, NLRP3 (NALP3). After 2 hours of incubation, monocytes display clear activation of caspase-1 regardless of LPS stimulation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="cleaved Caspase1*"/> <bbox w="80.0" h="40.0" x="5765.0" y="2350.0"/> <glyph class="unit of information" id="_c1b4b59b-0c6a-452c-b5ae-7e4765679465"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="5780.0" y="2345.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s1370_sa739"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: PYD and CARD domain containing HUGO:PYCARD hgnc_id:HGNC:16608 HGNC:16608 ENTREZ:29108 UNIPROT:Q9ULZ3 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19104081 Inflammasome is needfull for processing and release of IL-1beta in monocytes downstream of TLR2 or TLR4 signaling. It contains CASP1, Pycard, NLRP3 (NALP3) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PYCARD"/> <bbox w="80.0" h="40.0" x="5760.0" y="2395.0"/> </glyph> <glyph class="macromolecule" id="s1369_sa738"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: NLR family pyrin domain containing 3 HUGO:NLRP3 hgnc_id:HGNC:16400 HGNC:16400 ENTREZ:114548 UNIPROT:Q96P20 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19104081 Inflammasome is needfull for processing and release of IL-1beta in monocytes downstream of TLR2 or TLR4 signaling. It contains CASP1, Pycard, NLRP3 (NALP3) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="NLRP3"/> <bbox w="80.0" h="40.0" x="5760.0" y="2435.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2179_sa744"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 beta HUGO:IL1B hgnc_id:HGNC:5992 HGNC:5992 ENTREZ:3553 UNIPROT:P01584 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19767732 the TLR4 ligand HMGB1 and ATP, which are both released by tumor cells exposed to cytotoxic agents, act in concert to promote IL-1β secretion by DC ex vivo. The treatment of DC with oxidized ATP or anti-HMGB1-neutralizing antibodies prior to loading with dying tumor cells completely abolished IL-1β secretion. PMID:20086177 ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="trIL1B"/> <bbox w="80.0" h="40.0" x="6735.0" y="3090.0"/> <glyph class="unit of information" id="_150892c5-b22b-4cc8-87ae-fa205592616c"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="6750.0" y="3085.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2181_sa746"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: calreticulin HUGO:CALR hgnc_id:HGNC:1455 HGNC:1455 ENTREZ:811 UNIPROT:P27797 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 CALR (CRT or calreticulin) is a lectin specific for monoglucosylated N-linked glycans (17) that binds to the MHC class I molecule via its carbohydrate side chain. It also associates non-covalently with ERp57 in peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting PMID:23157435, PMID:16239148, PMID:20958319 CALR (CRT or calreticulin) is released by dying tumor cells and acts as eat-me signal. It acts via CD91 (LRP1) and initiates clearance of viable or apoptotic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CALR"/> <bbox w="80.0" h="40.0" x="3060.0" y="4085.0"/> </glyph> <glyph class="macromolecule" id="s2182_sa747" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: LDL receptor related protein 1 HUGO:LRP1 hgnc_id:HGNC:6692 HGNC:6692 ENTREZ:4035 UNIPROT:Q07954 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:25351513 Bright expression of CD91 identiﬁes highly activated human dendritic cells PMID:23157435, PMID:16239148 CALR (CRT or calreticulin) is released by dying tumor cells and acts as eat-me signal. It acts via CD91 (LRP1). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LRP1"/> <bbox w="80.0" h="50.0" x="2585.0" y="3625.0"/> <glyph class="unit of information" id="_41a38527-7811-4a04-9821-16964397aed8"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2602.5" y="3620.0"/> </glyph> </glyph> <glyph class="complex" id="s2184_csa114" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CALR:LRP1 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2184"/> <bbox w="100.0" h="120.0" x="2705.0" y="3590.0"/> <glyph class="macromolecule" id="s2186_sa745"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: calreticulin HUGO:CALR hgnc_id:HGNC:1455 HGNC:1455 ENTREZ:811 UNIPROT:P27797 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:16181333, PMID:22076556 CALR (CRT or calreticulin) is a lectin specific for monoglucosylated N-linked glycans (17) that binds to the MHC class I molecule via its carbohydrate side chain. It also associates non-covalently with ERp57 in peptide-loading complex. PMID:17204652 DCs, which are biased for MHCI cross-presentation, were enriched in Tap1, Tap2, calreticulin, calnexin, Sec61, ERp57, ERAAP, as well as cystatin B and C, all of which are involved in MHCI presentation or inhibition of enzymes that process peptides PMID:14508489 Together with TAP, tapasin, calreticulin, ERp57 and the heavy chain of MHC class I were all detected in purified early phagosomes by western blotting PMID:23157435, PMID:16239148, PMID:20958319 CALR (CRT or calreticulin) is released by dying tumor cells and acts as eat-me signal. It acts via CD91 (LRP1) and initiates clearance of viable or apoptotic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CALR"/> <bbox w="80.0" h="40.0" x="2715.0" y="3650.0"/> </glyph> <glyph class="macromolecule" id="s2185_sa748"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: LDL receptor related protein 1 HUGO:LRP1 hgnc_id:HGNC:6692 HGNC:6692 ENTREZ:4035 UNIPROT:Q07954 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:25351513 Bright expression of CD91 identiﬁes highly activated human dendritic cells PMID:23157435, PMID:16239148 CALR (CRT or calreticulin) is released by dying tumor cells and acts as eat-me signal. It acts via CD91 (LRP1). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LRP1"/> <bbox w="80.0" h="50.0" x="2715.0" y="3595.0"/> <glyph class="unit of information" id="_f1407e6a-87f6-41df-91ed-83b00db824a4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2732.5" y="3590.0"/> </glyph> </glyph> </glyph> <glyph class="phenotype" id="s2188_sa750" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PHAGOCYTOSIS"/> <bbox w="360.0" h="145.0" x="2615.0" y="3347.5"/> </glyph> <glyph class="macromolecule" id="s2189_sa751" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X3-C motif chemokine receptor 1 HUGO:CX3CR1 hgnc_id:HGNC:2558 HGNC:2558 ENTREZ:1524 UNIPROT:P49238 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:12455035 CX3CL1 induces chemoattraction and activation of DC via CX3CR1 and induces Tcell activation. Adherence of DC to cells expressed CX3CL1 resulted in phenotypic maturation and upregulated IL-12 secretion of DC, and more strong stimulation of allogeneic T-cell proliferation by DC PMID:11766992 Fractalkine induces chemotaxis and migration associated actin polymerization in immature as well as in mature DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text=" CX3CR1"/> <bbox w="80.0" h="50.0" x="2345.0" y="3325.0"/> <glyph class="unit of information" id="_fa2a74e3-6c7c-4bd7-82da-985b3f003f6f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2362.5" y="3320.0"/> </glyph> </glyph> <glyph class="complex" id="s2191_csa115" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME: CX3CR1:CX3CL1 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:11766992 Fractalkine via CX3CR1 induces chemotaxis and migration associated actin polymerization in immature as well as in mature DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2191"/> <bbox w="100.0" h="140.0" x="2455.0" y="3330.0"/> <glyph class="macromolecule" id="s2190_sa752"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: C-X3-C motif chemokine ligand 1 HUGO:CX3CL1 hgnc_id:HGNC:10647 HGNC:10647 ENTREZ:6376 UNIPROT:P78423 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:18799722 CX3CL1/fractalkine is released from dying cells PMID:18363071 Fractalkine (CX3CL1) is the only CX3C chemokine that can chemoattract natural killer (NK) cells, CD8+ T cells, monocytes, and dendritic cells. PMID:12455035 CX3CL1 induces chemoattraction and activation of DC via CX3CR1 and induces Tcell activation. Adherence of DC to cells expressed CX3CL1 resulted in phenotypic maturation and upregulated IL-12 secretion of DC, and more strong stimulation of allogeneic T-cell proliferation by DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CX3CL1"/> <bbox w="80.0" h="40.0" x="2465.0" y="3400.0"/> </glyph> <glyph class="macromolecule" id="s2192_sa753"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: C-X3-C motif chemokine receptor 1 HUGO:CX3CR1 hgnc_id:HGNC:2558 HGNC:2558 ENTREZ:1524 UNIPROT:P49238 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:12455035 CX3CL1 induces chemoattraction and activation of DC via CX3CR1 and induces Tcell activation. Adherence of DC to cells expressed CX3CL1 resulted in phenotypic maturation and upregulated IL-12 secretion of DC, and more strong stimulation of allogeneic T-cell proliferation by DC PMID:11766992 Fractalkine induces chemotaxis and migration associated actin polymerization in immature as well as in mature DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text=" CX3CR1"/> <bbox w="80.0" h="50.0" x="2465.0" y="3345.0"/> <glyph class="unit of information" id="_8dc05d41-3366-40da-bb14-8699853596de"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2482.5" y="3340.0"/> </glyph> </glyph> </glyph> <glyph class="phenotype" id="s858_sa756" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Actin polymerization"/> <bbox w="160.0" h="35.0" x="2405.0" y="2962.5"/> </glyph> <glyph class="macromolecule" id="s2193_sa757" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: sphingosine-1-phosphate receptor 1 HUGO:S1PR1 hgnc_id:HGNC:3165 HGNC:3165 ENTREZ:1901 UNIPROT:P21453 sphingosine-1-phosphate receptor 2 HUGO:S1PR2 hgnc_id:HGNC:3169 HGNC:3169 ENTREZ:9294 UNIPROT:O95136 sphingosine-1-phosphate receptor 3 HUGO:S1PR3 hgnc_id:HGNC:3167 HGNC:3167 ENTREZ:1903 UNIPROT:Q99500 sphingosine-1-phosphate receptor 4 HUGO:S1PR4 hgnc_id:HGNC:3170 HGNC:3170 ENTREZ:8698 UNIPROT:O95977 sphingosine-1-phosphate receptor 5 HUGO:S1PR5 hgnc_id:HGNC:14299 HGNC:14299 ENTREZ:53637 UNIPROT:Q9H228 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:11919175 Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. Immature and mature DC express the mRNA for different S1P receptors, such as endothelial differentiation gene (EDG)-1, EDG-3, EDG-5, and EDG-6. In immature DC, S1P stimulated pertussis toxin-sensitive Ca2+ increase actin polymerization and chemotaxis. These responses were lost by DC matured with lipopolysaccharide. In maturing DC, however, S1P inhibited the secretion of tumor necrosis References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="S1PR*"/> <bbox w="80.0" h="50.0" x="2285.0" y="3435.0"/> <glyph class="unit of information" id="_69223d43-ebfd-4197-affa-47b73d0c8860"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2302.5" y="3430.0"/> </glyph> </glyph> <glyph class="complex" id="s2195_csa116" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:S1PR*:Sphingosine 1-phosphate Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11919175 S1P induces Ca2+ mobilization, actin polymerization, and migration in immature, but not in LPS-differentiated DC. S1P reduces IL-12 and TNF-α production, and augments IL-10 release in maturing DC inhibiting their capacity to induce Th1 immune responses. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2195"/> <bbox w="200.0" h="120.0" x="2145.0" y="3170.0"/> <glyph class="macromolecule" id="s2196_sa758"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: sphingosine-1-phosphate receptor 1 HUGO:S1PR1 hgnc_id:HGNC:3165 HGNC:3165 ENTREZ:1901 UNIPROT:P21453 sphingosine-1-phosphate receptor 2 HUGO:S1PR2 hgnc_id:HGNC:3169 HGNC:3169 ENTREZ:9294 UNIPROT:O95136 sphingosine-1-phosphate receptor 3 HUGO:S1PR3 hgnc_id:HGNC:3167 HGNC:3167 ENTREZ:1903 UNIPROT:Q99500 sphingosine-1-phosphate receptor 4 HUGO:S1PR4 hgnc_id:HGNC:3170 HGNC:3170 ENTREZ:8698 UNIPROT:O95977 sphingosine-1-phosphate receptor 5 HUGO:S1PR5 hgnc_id:HGNC:14299 HGNC:14299 ENTREZ:53637 UNIPROT:Q9H228 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:11919175 Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. Immature and mature DC express the mRNA for different S1P receptors, such as endothelial differentiation gene (EDG)-1, EDG-3, EDG-5, and EDG-6. In immature DC, S1P stimulated pertussis toxin-sensitive Ca2+ increase actin polymerization and chemotaxis. These responses were lost by DC matured with lipopolysaccharide. In maturing DC, however, S1P inhibited the secretion of tumor necrosis References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="S1PR*"/> <bbox w="80.0" h="50.0" x="2205.0" y="3215.0"/> <glyph class="unit of information" id="_cc585313-3a5d-418b-997f-6daf506f8f59"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2222.5" y="3210.0"/> </glyph> </glyph> <glyph class="simple chemical" id="s2197_sa759"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> PMID:18362204 Apoptotic cells may up-regulate SphK1 to produce and secrete S1P that serves as a "come-and-get-me" signal for scavenger cells PMID:11919175 Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. Immature and mature DC express the mRNA for different S1P receptors, such as endothelial differentiation gene (EDG)-1, EDG-3, EDG-5, and EDG-6. In immature DC, S1P stimulated pertussis toxin-sensitive Ca2+ increase actin polymerization and chemotaxis. These responses were lost by DC matured with lipopolysaccharide. In maturing DC, however, S1P inhibited the secretion of tumor necrosis factor α and interleukin (IL)-12, whereas it enhanced secretion of IL-10. As a consequence, mature DC exposed to S1P showed a reduced and increased capacity to generate allogeneic Th1 and Th2 responses, respectively. In summary, our study implicates that S1P might regulate the trafficking of DC and ultimately favor Th2 lymphocyte-dominated immunity. </body> </html> </notes> <label text="Sphingosine 1-phosphate"/> <bbox w="175.0" h="32.5" x="2157.5" y="3183.75"/> </glyph> </glyph> <glyph class="simple chemical" id="s2198_sa760" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:16204312 Calcium influx is an early event during perforin-mediated cytotoxicity. PMID:12740575, PMID:15972651 NKG2D signaling inducese PLCG2 phosphorylation and Ca2+ release. The calcium signal generated by PLCG is required for NKG2D-initiated killing. Calcium influx is an early event during perforin-mediated cytotoxicity. PLC-γ2 is absolutely required to regulate degranulation of cytotoxic perforin granules. PMID:22683124 PLCG2-deficient NK cells displayed a partial reduction of conjugate formationwith target tumor cells probably via regulation of Ca2+ fluxes, because a chelator of intracellular Ca2+ also provokes a partial reduction of conjugate formation. PMID:11265639 Cross-linking of NKp80 induces Ca 2+ mobilization and triggering of cytotoxicity in both resting and activated NK cells. PMID:2536067, PMID:1281218 Ligation of Fc gamma RIII alpha (CD16) induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells and stimulates expression of many cytokines via Ca('2+) -depend mechanism. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Ca2+"/> <bbox w="25.0" h="25.0" x="4072.5" y="2837.5"/> </glyph> <glyph class="simple chemical" id="s2199_sa761"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22035837 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PtdSer"/> <bbox w="70.0" h="25.0" x="3175.0" y="4212.5"/> </glyph> <glyph class="complex" id="s2206_csa118" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ITGAV:ITGB3:MFGE8:PtdSer Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22035837, PMID:12000961 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes (directly demonstrated for macrophages only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2206"/> <bbox w="190.0" h="152.5" x="2820.0" y="3573.75"/> <glyph class="macromolecule" id="s2205_sa763"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit alpha V HUGO:ITGAV hgnc_id:HGNC:6150 HGNC:6150 ENTREZ:3685 UNIPROT:P06756 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGAV"/> <bbox w="80.0" h="50.0" x="2830.0" y="3588.75"/> <glyph class="unit of information" id="_dda4d51e-dfba-41ca-b601-8e002a23de59"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2847.5" y="3583.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s2207_sa764"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: milk fat globule-EGF factor 8 protein HUGO:MFGE8 hgnc_id:HGNC:7036 HGNC:7036 ENTREZ:4240 UNIPROT:Q08431 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:22035837, PMID:15031725 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes PMID:14697347, PMID: 11146654 The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells by DCs.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MFGE8"/> <bbox w="80.0" h="40.0" x="2920.0" y="3636.25"/> </glyph> <glyph class="simple chemical" id="s2208_sa765"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> PMID:22035837 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes </body> </html> </notes> <label text="PtdSer"/> <bbox w="70.0" h="25.0" x="2925.0" y="3683.75"/> </glyph> <glyph class="macromolecule" id="s2209_sa766"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit beta 3 HUGO:ITGB3 hgnc_id:HGNC:6156 HGNC:6156 ENTREZ:3690 UNIPROT:P05106 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGB3"/> <bbox w="80.0" h="50.0" x="2830.0" y="3633.75"/> <glyph class="unit of information" id="_43f67f75-3b6a-4ea9-bcf1-faa906f1dd46"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2847.5" y="3628.75"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2024_sa526" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: lymphotoxin alpha HUGO:LTA hgnc_id:HGNC:6709 HGNC:6709 ENTREZ:4049 UNIPROT:P01374 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:11823516 Human immature dendritic cells express on their cell surface four different cytotoxic TNF family ligands: TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis inducing ligand; while cancer cells express the corresponding death receptors. Disruptions of interactions between the four ligands expressed on DCs and corresponding death-signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion proteins block the cytotoxic activity of DCs directed against cancer cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LTA"/> <bbox w="80.0" h="40.0" x="3565.0" y="3420.0"/> </glyph> <glyph class="macromolecule" id="s2210_sa767" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: milk fat globule-EGF factor 8 protein HUGO:MFGE8 hgnc_id:HGNC:7036 HGNC:7036 ENTREZ:4240 UNIPROT:Q08431 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:22035837, PMID:15031725 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes PMID:14697347, PMID: 11146654 The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells by DCs.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MFGE8"/> <bbox w="80.0" h="40.0" x="3075.0" y="3650.0"/> </glyph> <glyph class="macromolecule" id="s2211_sa768" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: dedicator of cytokinesis 1 HUGO:DOCK1 hgnc_id:HGNC:2987 HGNC:2987 ENTREZ:1793 UNIPROT:Q14185 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="DOCK1"/> <bbox w="80.0" h="40.0" x="3095.0" y="3060.0"/> </glyph> <glyph class="complex" id="s2212_csa119" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:ITGAV:ITGB5:MFGE8:PtdSer Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2212"/> <bbox w="187.5" h="157.5" x="3171.25" y="3561.25"/> <glyph class="macromolecule" id="s2213_sa769"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: milk fat globule-EGF factor 8 protein HUGO:MFGE8 hgnc_id:HGNC:7036 HGNC:7036 ENTREZ:4240 UNIPROT:Q08431 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:22035837, PMID:15031725 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes PMID:14697347, PMID: 11146654 The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells by DCs.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MFGE8"/> <bbox w="80.0" h="40.0" x="3178.75" y="3618.75"/> </glyph> <glyph class="simple chemical" id="s2214_sa770"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> PMID:22035837 The ‘bridging’ molecule MFG-E8 (which binds to PtdSer on apoptotic cells and facilitate engulfment by engaging the integrin αvβ3 on phagocytes </body> </html> </notes> <label text="PtdSer"/> <bbox w="70.0" h="25.0" x="3186.25" y="3673.75"/> </glyph> <glyph class="macromolecule" id="s2215_sa771"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit alpha V HUGO:ITGAV hgnc_id:HGNC:6150 HGNC:6150 ENTREZ:3685 UNIPROT:P06756 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:9295024, PMID:9763615 Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36. The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGAV"/> <bbox w="80.0" h="50.0" x="3268.75" y="3573.75"/> <glyph class="unit of information" id="_0ca98fa0-d70b-4894-98ef-8f83d645064f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3286.25" y="3568.75"/> </glyph> </glyph> <glyph class="macromolecule" id="s2216_sa772"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: integrin subunit beta 5 HUGO:ITGB5 hgnc_id:HGNC:6160 HGNC:6160 ENTREZ:3693 UNIPROT:P18084 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ITGB5"/> <bbox w="80.0" h="50.0" x="3268.75" y="3623.75"/> <glyph class="unit of information" id="_22f16551-57f9-4211-80bf-a09c27a76c52"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3286.25" y="3618.75"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2217_sa773" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CRK proto-oncogene, adaptor protein HUGO:CRK hgnc_id:HGNC:2362 HGNC:2362 ENTREZ:1398 UNIPROT:P46108 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CRK"/> <bbox w="80.0" h="40.0" x="3195.0" y="3060.0"/> </glyph> <glyph class="macromolecule" id="s1388_sa774" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: BCAR1, Cas family scaffolding protein HUGO:BCAR1 hgnc_id:HGNC:971 HGNC:971 ENTREZ:9564 UNIPROT:P56945 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:11146654, PMID:14697347 alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells downstream of MFG-E8. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="BCAR1"/> <bbox w="80.0" h="40.0" x="3305.0" y="3060.0"/> <glyph class="state variable" id="_992b38c7-c004-49ee-8ed5-4c9eada4901f"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3300.0" y="3075.0"/> </glyph> </glyph> <glyph class="complex" id="s2221_csa120" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:BCAR1:CRK:DOCK1 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2221"/> <bbox w="200.0" h="150.0" x="3015.0" y="3115.0"/> <glyph class="macromolecule" id="s2223_sa775"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: BCAR1, Cas family scaffolding protein HUGO:BCAR1 hgnc_id:HGNC:971 HGNC:971 ENTREZ:9564 UNIPROT:P56945 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:11146654, PMID:14697347 alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells downstream of MFG-E8. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="BCAR1"/> <bbox w="80.0" h="40.0" x="3115.0" y="3135.0"/> <glyph class="state variable" id="_45ee2380-c62b-42d1-a0a8-b3d451ebbbde"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="3110.0" y="3150.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2222_sa776"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CRK proto-oncogene, adaptor protein HUGO:CRK hgnc_id:HGNC:2362 HGNC:2362 ENTREZ:1398 UNIPROT:P46108 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CRK"/> <bbox w="80.0" h="40.0" x="3025.0" y="3135.0"/> </glyph> <glyph class="macromolecule" id="s2220_sa777"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: dedicator of cytokinesis 1 HUGO:DOCK1 hgnc_id:HGNC:2987 HGNC:2987 ENTREZ:1793 UNIPROT:Q14185 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14697347, PMID: 11146654 Integrin αvβ5 regulates phagocytosis via CRK /DOCK1 (DOCK180) /RAC1 pathway downstream of. Integrin αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex and RAC1 activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="DOCK1"/> <bbox w="80.0" h="40.0" x="3075.0" y="3195.0"/> </glyph> </glyph> <glyph class="phenotype" id="s2227_sa781"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="KEEP OUT"/> <bbox w="210.0" h="115.0" x="1965.0" y="4067.5"/> </glyph> <glyph class="macromolecule" id="s2228_sa782" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal regulatory protein alpha HUGO:SIRPA hgnc_id:HGNC:9662 HGNC:9662 ENTREZ:140885 UNIPROT:P78324 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11509594 CD47 binds SIRP-α on DC. SIRP-α engagement down-regulates DC function CD47-Fc potently suppressed IL-12 and TNF-α release by monocyte-derived DC stimulated by SAC. The inhibitory effect was dose dependent, and significant suppression was seen with as little as 10 ng/ml CD47-Fc (Fig. 5⇓B). Other cytokines, including IL-6 and IL-10, were also suppressed, CD47-Fc not only suppressed cytokine release by maturing DC, but also largely prevented DC phenotypic maturation. As indicated in Fig. 6⇓, CD83 and CD86 up-regulation were strongly reduced regardless of the stimulus used. For CD80, the inhibition was almost complete in response to CD40 signaling, moderate in response to SAC, and modest, but significant in response to LPS. CD40 expression was weakly up-regulated during DC maturation. In all three conditions, SIRP-α ligation by CD47-Fc abrogated the CD40 increase. Note only a slight reduction in HLA-DR expression. All together, these results demonstrate that engagement of SIRP-α largely inhibits DC maturation References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SIRPA"/> <bbox w="80.0" h="50.0" x="1935.0" y="3235.0"/> <glyph class="unit of information" id="_3d605319-53f9-410a-bfa8-75becf59cb5a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1952.5" y="3230.0"/> </glyph> </glyph> <glyph class="complex" id="s2229_csa121" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CD47:SIRPA Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2229"/> <bbox w="120.0" h="180.0" x="1785.0" y="3310.0"/> <glyph class="macromolecule" id="s2235_sa783"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: signal regulatory protein alpha HUGO:SIRPA hgnc_id:HGNC:9662 HGNC:9662 ENTREZ:140885 UNIPROT:P78324 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11509594 CD47 binds SIRP-α on DC. SIRP-α engagement down-regulates DC function CD47-Fc potently suppressed IL-12 and TNF-α release by monocyte-derived DC stimulated by SAC. The inhibitory effect was dose dependent, and significant suppression was seen with as little as 10 ng/ml CD47-Fc (Fig. 5⇓B). Other cytokines, including IL-6 and IL-10, were also suppressed, CD47-Fc not only suppressed cytokine release by maturing DC, but also largely prevented DC phenotypic maturation. As indicated in Fig. 6⇓, CD83 and CD86 up-regulation were strongly reduced regardless of the stimulus used. For CD80, the inhibition was almost complete in response to CD40 signaling, moderate in response to SAC, and modest, but significant in response to LPS. CD40 expression was weakly up-regulated during DC maturation. In all three conditions, SIRP-α ligation by CD47-Fc abrogated the CD40 increase. Note only a slight reduction in HLA-DR expression. All together, these results demonstrate that engagement of SIRP-α largely inhibits DC maturation References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SIRPA"/> <bbox w="80.0" h="50.0" x="1805.0" y="3325.0"/> <glyph class="unit of information" id="_b272cb33-4a5c-4574-a556-04f3b2b0db30"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1822.5" y="3320.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2236_sa784"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD47 molecule HUGO:CD47 hgnc_id:HGNC:1682 HGNC:1682 ENTREZ:961 UNIPROT:Q08722 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11509594 CD47 binds SIRP-α on DC. SIRP-α engagement down-regulates DC function CD47-Fc potently suppressed IL-12 and TNF-α release by monocyte-derived DC stimulated by SAC. The inhibitory effect was dose dependent, and significant suppression was seen with as little as 10 ng/ml CD47-Fc (Fig. 5⇓B). Other cytokines, including IL-6 and IL-10, were also suppressed, CD47-Fc not only suppressed cytokine release by maturing DC, but also largely prevented DC phenotypic maturation. As indicated in Fig. 6⇓, CD83 and CD86 up-regulation were strongly reduced regardless of the stimulus used. For CD80, the inhibition was almost complete in response to CD40 signaling, moderate in response to SAC, and modest, but significant in response to LPS. CD40 expression was weakly up-regulated during DC maturation. In all three conditions, SIRP-α ligation by CD47-Fc abrogated the CD40 increase. Note only a slight reduction in HLA-DR expression. All together, these results demonstrate that engagement of SIRP-α largely inhibits DC maturation. PMID:10657674, PMID:10657674 CD47 is expresed on dendritic cells PMID:10657674, PMID:14568985 CD47 engagement by Thrombospondin-1 inhibits cytokine production and maturation of human dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD47"/> <bbox w="80.0" h="50.0" x="1805.0" y="3385.0"/> <glyph class="unit of information" id="_9de8823f-d02f-47c9-b82e-fe53f48de770"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1822.5" y="3380.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s2238_csa122" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CD47:THBS1 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10657674 CD47 engagement by Thrombospondin-1 peptide inhibits cytokine production and maturation of human dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2229"/> <bbox w="105.0" h="140.0" x="2115.0" y="3400.0"/> <glyph class="macromolecule" id="s2237_sa789"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: thrombospondin 1 HUGO:THBS1 hgnc_id:HGNC:11785 HGNC:11785 ENTREZ:7057 UNIPROT:P07996 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14996710 Thrombospondin-1 is associated with tumor microenvironment. PMID:10657674 CD47 engagement by Thrombospondin-1 peptide inhibits cytokine production and maturation of human dendritic cells. PMID:14568985 Thrombospondin 1 is an autocrine negative regulator of human dendritic cell activation. The endogenous TSP produced during early DC activation negatively regulates IL-12, TNF-α, and IL-10 release through its interactions with CD47. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="THBS1"/> <bbox w="80.0" h="40.0" x="2130.0" y="3470.0"/> </glyph> <glyph class="macromolecule" id="s5065_sa976"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: CD47 molecule HUGO:CD47 hgnc_id:HGNC:1682 HGNC:1682 ENTREZ:961 UNIPROT:Q08722 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11509594 CD47 binds SIRP-α on DC. SIRP-α engagement down-regulates DC function CD47-Fc potently suppressed IL-12 and TNF-α release by monocyte-derived DC stimulated by SAC. The inhibitory effect was dose dependent, and significant suppression was seen with as little as 10 ng/ml CD47-Fc (Fig. 5⇓B). Other cytokines, including IL-6 and IL-10, were also suppressed, CD47-Fc not only suppressed cytokine release by maturing DC, but also largely prevented DC phenotypic maturation. As indicated in Fig. 6⇓, CD83 and CD86 up-regulation were strongly reduced regardless of the stimulus used. For CD80, the inhibition was almost complete in response to CD40 signaling, moderate in response to SAC, and modest, but significant in response to LPS. CD40 expression was weakly up-regulated during DC maturation. In all three conditions, SIRP-α ligation by CD47-Fc abrogated the CD40 increase. Note only a slight reduction in HLA-DR expression. All together, these results demonstrate that engagement of SIRP-α largely inhibits DC maturation. PMID:10657674, PMID:10657674 CD47 is expresed on dendritic cells PMID:10657674, PMID:14568985 CD47 engagement by Thrombospondin-1 inhibits cytokine production and maturation of human dendritic cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD47"/> <bbox w="80.0" h="50.0" x="2130.0" y="3415.0"/> <glyph class="unit of information" id="_cffcf7c7-e8a3-4762-95a9-8ff8027d83cc"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2147.5" y="3410.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2240_sa790"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: thrombospondin 1 HUGO:THBS1 hgnc_id:HGNC:11785 HGNC:11785 ENTREZ:7057 UNIPROT:P07996 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:14996710 Thrombospondin-1 is associated with tumor microenvironment. PMID:10657674 CD47 engagement by Thrombospondin-1 peptide inhibits cytokine production and maturation of human dendritic cells. PMID:14568985 Thrombospondin 1 is an autocrine negative regulator of human dendritic cell activation. The endogenous TSP produced during early DC activation negatively regulates IL-12, TNF-α, and IL-10 release through its interactions with CD47. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="THBS1"/> <bbox w="80.0" h="40.0" x="2030.0" y="3935.0"/> </glyph> <glyph class="phenotype" id="s2244_sa793" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="DC markers"/> <bbox w="170.0" h="55.0" x="6260.0" y="3252.5"/> </glyph> <glyph class="phenotype" id="s2245_sa794"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22437870 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Immune checkpoints_T_cells_Activators"/> <bbox w="295.0" h="80.0" x="5917.5" y="3630.0"/> </glyph> <glyph class="phenotype" id="s2246_sa795" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22437870 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Immune checkpoints_T_cells_Inhibitors"/> <bbox w="290.0" h="75.0" x="790.0" y="3152.5"/> </glyph> <glyph class="macromolecule" id="s2247_sa796" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD274 molecule HUGO:CD274 hgnc_id:HGNC:17635 HGNC:17635 ENTREZ:29126 UNIPROT:Q9NZQ7 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:24076050,PMID:12538684 PDL1 and PDL2 are expressed in DCs. blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PDL1*"/> <bbox w="80.0" h="40.0" x="745.0" y="2900.0"/> </glyph> <glyph class="macromolecule" id="s2248_sa797" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: programmed cell death 1 ligand 2 HUGO:PDCD1LG2 hgnc_id:HGNC:18731 HGNC:18731 ENTREZ:80380 UNIPROT:Q9BQ51 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:24076050,PMID:12538684 PDL1 and PDL2 are expressed in DCs. blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="PDL2*"/> <bbox w="80.0" h="40.0" x="845.0" y="2900.0"/> </glyph> <glyph class="macromolecule" id="s2249_sa798" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inducible T-cell costimulator ligand HUGO:ICOSLG hgnc_id:HGNC:17087 HGNC:17087 ENTREZ:23308 UNIPROT:O75144 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:11007762 ICOSLG (B7RP1) is expressed on PB B cells and monocytes, and on PB monocyte-derived DC. It is the ligand to the co-stimulatory protein ICOS of T cells. PMID:17200410, PMID:23125331 pDCs stimulated with IL-3 plus CD40L gradually up-regulated CD80 and CD86 expression and became fully mature DCs within 6 d of culturing. In contrast, the up-regulation of ICOS-L was very strong and occurred very rapidly (reaching log 2–3 fluorescence intensity within the first 24 h of culturing. PMID:23026134 ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ICOSLG"/> <bbox w="80.0" h="40.0" x="5525.0" y="3330.0"/> </glyph> <glyph class="macromolecule" id="s2250_sa800" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD276 molecule HUGO:CD276 hgnc_id:HGNC:19137 HGNC:19137 ENTREZ:80381 UNIPROT:Q5ZPR3 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:17615586, PMID:15294965 After contact to Treg, DC up-regulate the inhibitory B7-H3 molecule and display reduced numbers of MHC–peptide complexes, leading to impaired T cell stimulatory function. B7-H3 plays a significant role in suppressing T cell activation by Treg-exposed DC. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B7H3*"/> <bbox w="80.0" h="40.0" x="945.0" y="2900.0"/> </glyph> <glyph class="macromolecule" id="s2251_sa801" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: V-set domain containing T-cell activation inhibitor 1 HUGO:VTCN1 hgnc_id:HGNC:28873 HGNC:28873 ENTREZ:79679 UNIPROT:Q7Z7D3 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:12818165 Freshly isolated human T cells, B cells, monocytes, and DC do not express B7-H4 on cell surface in FACS analysis. In contrast, B7-H4 expression can be induced on T cells, B cells, monocytes, and DC after in vitro stimulation B7H4 inhibits T-cell response. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B7H4*"/> <bbox w="80.0" h="40.0" x="1045.0" y="2900.0"/> </glyph> <glyph class="macromolecule" id="s2252_sa802" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF receptor superfamily member 14 HUGO:TNFRSF14 hgnc_id:HGNC:11912 HGNC:11912 ENTREZ:8764 UNIPROT:Q92956 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:18097025 HVEM is expressed in DCs. PMID:18193050 Binding of HVEM to BTLA or CD160 inhibited T cell activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="HVEM*"/> <bbox w="80.0" h="40.0" x="1165.0" y="2900.0"/> </glyph> <glyph class="macromolecule" id="s2253_sa804" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 9 HUGO:TNFSF9 hgnc_id:HGNC:11939 HGNC:11939 ENTREZ:8744 UNIPROT:P41273 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:8992967, PMID:16288496 TNFSF9 (CD137L, 4-1BBL) is expressed in DCs and induces T-cell activation adn inhibits tumor growth. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TNFSF9"/> <bbox w="80.0" h="40.0" x="5415.0" y="3330.0"/> </glyph> <glyph class="macromolecule" id="s2254_sa805" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 4 HUGO:TNFSF4 hgnc_id:HGNC:11934 HGNC:11934 ENTREZ:7292 UNIPROT:P23510 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:9378971, PMID:10626891 OX40L is expressed on DCs surface after CD40 stimulation. Ox40L-deficient dendritic cells are defective in costimulating T cell cytokine production PMID:15034038 pDCs stimulated with IL-3 plus CD40L expressed OX40L (mRNA and protein), but produced almost no IFN-alpha in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. PMID:24778133 Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL (). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="OX40L*"/> <bbox w="80.0" h="40.0" x="5305.0" y="3330.0"/> </glyph> <glyph class="macromolecule" id="s2255_sa806" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 4 HUGO:TNFSF4 hgnc_id:HGNC:11934 HGNC:11934 ENTREZ:7292 UNIPROT:P23510 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:9378971, PMID:10626891 OX40L is expressed on DCs surface after CD40 stimulation. Ox40L-deficient dendritic cells are defective in costimulating T cell cytokine production PMID:15034038 pDCs stimulated with IL-3 plus CD40L expressed OX40L (mRNA and protein), but produced almost no IFN-alpha in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. PMID:24778133 Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL (). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="OX40L*"/> <bbox w="80.0" h="40.0" x="5285.0" y="3100.0"/> </glyph> <glyph class="macromolecule" id="s2263_sa809" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD70 molecule HUGO:CD70 hgnc_id:HGNC:11937 HGNC:11937 ENTREZ:970 UNIPROT:P32970 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:19062317, PMID:17237405 CD70 is a costimulatory ligand acquired upon DC maturation. It stimulates T-cells and provides tumor regression. PMID:17237405 Surface expression of CD70 in DC is TLR and CD40 dependent. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD70"/> <bbox w="80.0" h="40.0" x="5635.0" y="3330.0"/> </glyph> <glyph class="macromolecule" id="s2264_sa810" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD70 molecule HUGO:CD70 hgnc_id:HGNC:11937 HGNC:11937 ENTREZ:970 UNIPROT:P32970 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:19062317, PMID:17237405 CD70 is a costimulatory ligand acquired upon DC maturation. It stimulates T-cells and provides tumor regression. PMID:17237405 Surface expression of CD70 in DC is TLR and CD40 dependent. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD70"/> <bbox w="80.0" h="40.0" x="5515.0" y="3020.0"/> </glyph> <glyph class="macromolecule" id="s2265_sa811" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: galectin 9 HUGO:LGALS9 hgnc_id:HGNC:6570 HGNC:6570 ENTREZ:3965 UNIPROT:O00182 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:22505239, PMID:16286920 Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. There are different levels of galectin-9 expression on antigen-presenting cell (APC) subsets including Kupffer cells (KCs), myeloid dendritic cells (DCs), and plasmacytoid DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LGALS9"/> <bbox w="80.0" h="40.0" x="1015.0" y="2810.0"/> </glyph> <glyph class="nucleic acid feature" id="s2266_sa812" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X-C motif chemokine ligand 10 HUGO:CXCL10 hgnc_id:HGNC:10637 HGNC:10637 ENTREZ:3627 UNIPROT:P02778 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11477091 TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-γ inducible protein (IP)-10 (CXCL10), which is also associated to Th1 responses PMID:11698286 IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCL10"/> <bbox w="70.0" h="25.0" x="5680.0" y="1717.5"/> </glyph> <glyph class="nucleic acid feature" id="s2267_sa813" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X-C motif chemokine ligand 10 HUGO:CXCL10 hgnc_id:HGNC:10637 HGNC:10637 ENTREZ:3627 UNIPROT:P02778 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:11477091 TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-γ inducible protein (IP)-10 (CXCL10), which is also associated to Th1 responses References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCL10"/> <bbox w="90.0" h="25.0" x="5670.0" y="1807.5"/> <glyph class="unit of information" id="_c56f7059-967a-4282-a838-0295f90c7979"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5705.0" y="1802.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2268_sa814"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-X-C motif chemokine ligand 10 HUGO:CXCL10 hgnc_id:HGNC:10637 HGNC:10637 ENTREZ:3627 UNIPROT:P02778 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:11477091 TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-γ inducible protein (IP)-10 (CXCL10), which is also associated to Th1 responses References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CXCL10"/> <bbox w="80.0" h="40.0" x="6815.0" y="3010.0"/> </glyph> <glyph class="macromolecule" id="s652_sa818" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 HUGO:MAP3K7 hgnc_id:HGNC:6859 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14660645, PMID:18264787, PMID:12620219 IRAK-1 interacts with the downstream adaptor TRAF6, resulting in formation of a complex that also includes TAK1 and TAB2. IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol, where they form a multiprotein complex with other cytosolic proteins, which are needed for stimulation of TAK1 kinase activity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MAP3K7"/> <bbox w="80.0" h="40.0" x="5115.0" y="1080.0"/> </glyph> <glyph class="complex" id="s651_csa123" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MAP3K7:TAB2/3* Identifiers_end Maps_Modules_begin: MODULE:DC Maps_Modules_end References_begin: PMID:23681101 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s651"/> <bbox w="100.0" h="130.0" x="4885.0" y="825.0"/> <glyph class="macromolecule" id="s646_sa820"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: mitogen-activated protein kinase kinase kinase 7 HUGO:MAP3K7 hgnc_id:HGNC:6859 HGNC:6859 ENTREZ:6885 UNIPROT:O43318 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14660645, PMID:18264787, PMID:12620219 IRAK-1 interacts with the downstream adaptor TRAF6, resulting in formation of a complex that also includes TAK1 and TAB2. IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol, where they form a multiprotein complex with other cytosolic proteins, which are needed for stimulation of TAK1 kinase activity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MAP3K7"/> <bbox w="80.0" h="40.0" x="4895.0" y="840.0"/> </glyph> <glyph class="macromolecule" id="s2273_sa824"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: TGF-beta activated kinase 1/MAP3K7 binding protein 2 HUGO:TAB2 hgnc_id:HGNC:17075 HGNC:17075 ENTREZ:23118 UNIPROT:Q9NYJ8 TGF-beta activated kinase 1 and MAP3K7 binding protein 3 HUGO:TAB3 hgnc_id:HGNC:30681 HGNC:30681 ENTREZ:257397 UNIPROT:Q8N5C8 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:18264787, PMID:12620219 IRAK-1 interacts with the downstream adaptor TRAF6, resulting in formation of a complex that also includes TAK1 and TAB2. IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol, where they form a multiprotein complex with other cytosolic proteins, which are needed for stimulation of TAK1 kinase activity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAB2/3*"/> <bbox w="80.0" h="40.0" x="4895.0" y="890.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2272_sa823" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TGF-beta activated kinase 1/MAP3K7 binding protein 2 HUGO:TAB2 hgnc_id:HGNC:17075 HGNC:17075 ENTREZ:23118 UNIPROT:Q9NYJ8 TGF-beta activated kinase 1 and MAP3K7 binding protein 3 HUGO:TAB3 hgnc_id:HGNC:30681 HGNC:30681 ENTREZ:257397 UNIPROT:Q8N5C8 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:18264787, PMID:12620219 IRAK-1 interacts with the downstream adaptor TRAF6, resulting in formation of a complex that also includes TAK1 and TAB2. IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol, where they form a multiprotein complex with other cytosolic proteins, which are needed for stimulation of TAK1 kinase activity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TAB2/3*"/> <bbox w="80.0" h="40.0" x="5115.0" y="1020.0"/> </glyph> <glyph class="macromolecule" id="s641_sa825" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 receptor associated kinase 1 HUGO:IRAK1 hgnc_id:HGNC:6112 HGNC:6112 ENTREZ:3654 UNIPROT:P51617 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12620219 MyD88 mediates a close interaction of the two related IRAK molecules, which is essential to allow IRAK-4 to phosphorylate IRAK-1. Phosphorylation of IRAK-1 reduces its affinity for MyD88, while increasing its affinity for TRAF6. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRAK1"/> <bbox w="80.0" h="40.0" x="5795.0" y="1080.0"/> <glyph class="state variable" id="_e3ada816-479a-4043-96a1-25cb65bba28b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="5790.0" y="1095.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s669_sa826" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 receptor associated kinase 1 HUGO:IRAK1 hgnc_id:HGNC:6112 HGNC:6112 ENTREZ:3654 UNIPROT:P51617 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12620219 MyD88 mediates a close interaction of the two related IRAK molecules, which is essential to allow IRAK-4 to phosphorylate IRAK-1. Phosphorylation of IRAK-1 reduces its affinity for MyD88, while increasing its affinity for TRAF6. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRAK1"/> <bbox w="80.0" h="40.0" x="5595.0" y="1070.0"/> <glyph class="state variable" id="_8972d6d8-f452-4b8b-88b8-ed73429fc41e"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="5587.5" y="1085.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s644_sa827" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF receptor associated factor 6 HUGO:TRAF6 hgnc_id:HGNC:12036 HGNC:12036 ENTREZ:7189 UNIPROT:Q9Y4K3 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:18264787, PMID:12620219 IRAK-1 interacts with the downstream adaptor TRAF6, resulting in formation of a complex that also includes TAK1 and TAB2. IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol, where they form a multiprotein complex with other cytosolic proteins, which are needed for stimulation of TAK1 kinase activity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAF6"/> <clone/> <bbox w="80.0" h="40.0" x="5595.0" y="990.0"/> </glyph> <glyph class="macromolecule" id="s644_sa828" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF receptor associated factor 6 HUGO:TRAF6 hgnc_id:HGNC:12036 HGNC:12036 ENTREZ:7189 UNIPROT:Q9Y4K3 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:18264787, PMID:12620219 IRAK-1 interacts with the downstream adaptor TRAF6, resulting in formation of a complex that also includes TAK1 and TAB2. IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol, where they form a multiprotein complex with other cytosolic proteins, which are needed for stimulation of TAK1 kinase activity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAF6"/> <clone/> <bbox w="80.0" h="40.0" x="5433.75" y="987.5"/> </glyph> <glyph class="macromolecule" id="s1158_sa829" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 2 receptor subunit alpha HUGO:IL2RA hgnc_id:HGNC:6008 HGNC:6008 ENTREZ:3559 UNIPROT:P01589 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10849428 IL-2 and IL-15 are able to induce the phosphorylation of ERK1/2. probably via PI3K pathway. MKK/ERK pathway is necessary for IL-2 to activate NK cells to express at least four known biological responses: LAK generation, IFN-gamma secretion, and IL2RA (CD25) and CLEC2C(CD69) expression. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RA"/> <bbox w="80.0" h="50.0" x="6225.0" y="1685.0"/> <glyph class="unit of information" id="_3293b8b8-f255-4967-a714-7b287a8caf47"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6242.5" y="1680.0"/> </glyph> </glyph> <glyph class="complex" id="s2275_csa124" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL2RA:IL2RB:IL2RG Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2275"/> <bbox w="207.5" h="140.0" x="6701.25" y="1700.0"/> <glyph class="macromolecule" id="s2354_sa830"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit alpha HUGO:IL2RA hgnc_id:HGNC:6008 HGNC:6008 ENTREZ:3559 UNIPROT:P01589 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10849428 IL-2 and IL-15 are able to induce the phosphorylation of ERK1/2. probably via PI3K pathway. MKK/ERK pathway is necessary for IL-2 to activate NK cells to express at least four known biological responses: LAK generation, IFN-gamma secretion, and IL2RA (CD25) and CLEC2C(CD69) expression. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RA"/> <bbox w="80.0" h="50.0" x="6706.25" y="1705.0"/> <glyph class="unit of information" id="_18bf93db-1a66-4368-aa1c-5127212674b2"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6723.75" y="1700.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2355_sa832"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit beta HUGO:IL2RB hgnc_id:HGNC:6009 HGNC:6009 ENTREZ:3560 UNIPROT:P14784 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16212621 IL-2- and IL-15-induced phosphorylation of the IL-2RB chain in T cells. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RB"/> <bbox w="80.0" h="50.0" x="6806.25" y="1705.0"/> <glyph class="state variable" id="_0a9fa144-f622-45cb-a7f9-625955a5e9a2"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6801.25" y="1725.0"/> </glyph> <glyph class="unit of information" id="_eae83a3a-a916-4183-bee7-4053478fa60f"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6823.75" y="1700.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2356_sa833"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit gamma HUGO:IL2RG hgnc_id:HGNC:6010 HGNC:6010 ENTREZ:3561 UNIPROT:P31785 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RG"/> <bbox w="80.0" h="50.0" x="6708.75" y="1755.0"/> <glyph class="unit of information" id="_1fdb1854-7b46-49f7-b390-3ae3ad03ec67"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6726.25" y="1750.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2280_sa834" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: fms related tyrosine kinase 3 HUGO:FLT3 hgnc_id:HGNC:3765 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15253381 It was found that the following signal transduction molecules were all activated by the stimulated FLT3 receptor: phospholipase g-1, RAS GTPase-activating protein GAP, p85 subunit of phosphatidylinositol 3-kinase (PI3 K), SH2-containing sequence proteins (SHCS), SH2-domain-containing inositol phosphatase (SHIP), GRB2, VAV, FYN and SRC. Of these, various molecules were shown to directly physically asssociate with the FLT3 cytoplasmic domain. These proteins are involved in different signal transduction pathways, including the RAS-RAF-MEK-ERK pathway References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT3"/> <bbox w="80.0" h="50.0" x="3965.0" y="605.0"/> <glyph class="unit of information" id="_79914053-26e7-44b9-be3d-8f16da72c895"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3982.5" y="600.0"/> </glyph> </glyph> <glyph class="complex" id="s2281_csa125" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:FLT3:FLT3LG Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2281"/> <bbox w="100.0" h="140.0" x="3895.0" y="400.0"/> <glyph class="macromolecule" id="s2282_sa835"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: fms related tyrosine kinase 3 HUGO:FLT3 hgnc_id:HGNC:3765 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15253381 It was found that the following signal transduction molecules were all activated by the stimulated FLT3 receptor: phospholipase g-1, RAS GTPase-activating protein GAP, p85 subunit of phosphatidylinositol 3-kinase (PI3 K), SH2-containing sequence proteins (SHCS), SH2-domain-containing inositol phosphatase (SHIP), GRB2, VAV, FYN and SRC. Of these, various molecules were shown to directly physically asssociate with the FLT3 cytoplasmic domain. These proteins are involved in different signal transduction pathways, including the RAS-RAF-MEK-ERK pathway References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT3"/> <bbox w="80.0" h="50.0" x="3905.0" y="465.0"/> <glyph class="unit of information" id="_43893697-d8b3-43ad-8617-e73d2e8dfc0a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3922.5" y="460.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2283_sa836"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: fms related tyrosine kinase 3 ligand HUGO:FLT3LG hgnc_id:HGNC:3766 HGNC:3766 ENTREZ:2323 UNIPROT:P49771 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10477595, PMID:9268501, PMID:8920882 The cytokine FLT3 ligand (FL) enhances dendritic cell (DC) generation and differentiation. PMID:10477595 FL induces Ag-presenting ability of DCs. FL induced a high level of NF-κB nuclear translocation and specific DNA binding VEGF inhibited FL-inducible activation of transcription factor NF-κB. PMID:14670306 STAT3 is required for Flt3L-dependent dendritic cell differentiation. 9176488 Flt3L treatment not only induced complete tumor regression in a significant proportion of mice, but also decreased tumor growth rate in the remaining mice. Probabli via DC activation. PMID:16418395 Activation of the Flt3 signal transduction cascade rescues and enhances type I interferon-producing and dendritic cell development. PMID:8920882 Daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers-class II MHC, CD11c, DEC205, and CD86. FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. PMID:25215878 FLT3L partially antagonized IL-10-mediated inhibition on DCs function and downregulates IL10 mRNA expression in DCs PMID:10477595, PMID:8920882, PMID:25215878 FLT3L induces Ag-presenting ability of Dcs. Probably via induction of surface expression of class II MHC and CD86 and also expression of CD83, a and CD80 and was significantly enhanced by the FLT3L Daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers CD11c, DEC205. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT3LG"/> <bbox w="80.0" h="40.0" x="3905.0" y="420.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2285_sa838"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 3 HUGO:IL3 hgnc_id:HGNC:6011 HGNC:6011 ENTREZ:3562 UNIPROT:P08700 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15549123 IL3 signaling is important for plasmacytoid DC which are expressing IL3RA. PMID:23762788 Tumor-infiltrating plasmacytoid dendritic cells (pDCs) have been associated with poor patient prognosis. PMID: 17200410, PMID:23125331, PMID:15034038 pDCs stimulated with IL-3 plus CD40L induce expression ICOS-L and OX40L. PMID:24778133, PMID:23026134 Expression ot ICOS-L and OX40L ligands by pDC promotes tumor progression by Promoting Th2 and Regulatory Immunity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL3"/> <bbox w="80.0" h="40.0" x="1525.0" y="460.0"/> </glyph> <glyph class="macromolecule" id="s2288_sa841" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Spi-1 proto-oncogene HUGO:SPI1 hgnc_id:HGNC:11241 HGNC:11241 ENTREZ:6688 UNIPROT:P17947 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:20510871 SPI1 (PU.1) is a critical regulator of both conventional and plasmacytoid DC development. It is directly upregulates Flt3 gene activation. PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SPI1"/> <bbox w="80.0" h="40.0" x="4135.0" y="980.0"/> </glyph> <glyph class="macromolecule" id="s2289_sa842" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: lymphocyte antigen 75 HUGO:LY75 hgnc_id:HGNC:6729 HGNC:6729 ENTREZ:4065 UNIPROT:O60449 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:10784619 LY75 (DEC-205) it is a a marker of dendritic cells with regulatory effects on CD8 T cell responses. PMID:8920882 FLT3 ligand upregulates surface expression of LY75 (DEC-205) in DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LY75"/> <bbox w="80.0" h="50.0" x="6245.0" y="2925.0"/> <glyph class="unit of information" id="_60e82a43-55df-44c7-9a31-678aecd5b614"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6262.5" y="2920.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2290_sa843" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: lymphocyte antigen 75 HUGO:LY75 hgnc_id:HGNC:6729 HGNC:6729 ENTREZ:4065 UNIPROT:O60449 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:10784619 LY75 (DEC-205) it is a a marker of dendritic cells with regulatory effects on CD8 T cell responses. PMID:8920882 FLT3 ligand upregulates surface expression of LY75 (DEC-205) in DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="LY75"/> <bbox w="80.0" h="50.0" x="6105.0" y="2665.0"/> <glyph class="unit of information" id="_78984523-59ac-4feb-8743-d4fb917c3d19"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="6122.5" y="2660.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2294_sa847" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: fms related tyrosine kinase 3 HUGO:FLT3 hgnc_id:HGNC:3765 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15253381 It was found that the following signal transduction molecules were all activated by the stimulated FLT3 receptor: phospholipase g-1, RAS GTPase-activating protein GAP, p85 subunit of phosphatidylinositol 3-kinase (PI3 K), SH2-containing sequence proteins (SHCS), SH2-domain-containing inositol phosphatase (SHIP), GRB2, VAV, FYN and SRC. Of these, various molecules were shown to directly physically asssociate with the FLT3 cytoplasmic domain. These proteins are involved in different signal transduction pathways, including the RAS-RAF-MEK-ERK pathway References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT3"/> <bbox w="80.0" h="50.0" x="3965.0" y="705.0"/> <glyph class="unit of information" id="_1d586599-8851-4237-9f7a-bca02511ff9b"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3982.5" y="700.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2295_sa848" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: fms related tyrosine kinase 3 HUGO:FLT3 hgnc_id:HGNC:3765 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:20510871 PU.1 as a critical regulator of both conventional and plasmacytoid DC development. It is directly upregulates Flt3 gene activation. PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. At The same time enforced expression of STAT3 or PU.1 in DC progenitors led to the up-regulation of Flt3 mRNA levels, so there is a positive loop in this signaling. Enforced STAT3 or PU.1 expression instructs progenitors to differentiate into Dcs. Additionaly it induces expression of cytokine receptors for G-CSF, M-CSF, and GM-CSF probably downstream of STAT3. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT3"/> <bbox w="70.0" h="25.0" x="3940.0" y="857.5"/> </glyph> <glyph class="nucleic acid feature" id="s2296_sa849" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: fms related tyrosine kinase 3 HUGO:FLT3 hgnc_id:HGNC:3765 HGNC:3765 ENTREZ:2322 UNIPROT:P36888 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:20510871 PU.1 as a critical regulator of both conventional and plasmacytoid DC development. It is directly upregulates Flt3 gene activation. PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. At The same time enforced expression of STAT3 or PU.1 in DC progenitors led to the up-regulation of Flt3 mRNA levels, so there is a positive loop in this signaling. Enforced STAT3 or PU.1 expression instructs progenitors to differentiate into Dcs. Additionaly it induces expression of cytokine receptors for G-CSF, M-CSF, and GM-CSF probably downstream of STAT3. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT3"/> <bbox w="90.0" h="25.0" x="3930.0" y="787.5"/> <glyph class="unit of information" id="_b2c723aa-4a77-4cbc-af2c-4bb00977fe0e"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3965.0" y="782.5"/> </glyph> </glyph> <glyph class="complex" id="s2297_csa126" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:GATA1:SPI1 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10753833 GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2297"/> <bbox w="100.0" h="120.0" x="4115.0" y="1080.0"/> <glyph class="macromolecule" id="s2298_sa850"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: GATA binding protein 1 HUGO:GATA1 hgnc_id:HGNC:4170 HGNC:4170 ENTREZ:2623 UNIPROT:P15976 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10753833 GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GATA1"/> <bbox w="80.0" h="40.0" x="4125.0" y="1090.0"/> </glyph> <glyph class="macromolecule" id="s2299_sa851"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Spi-1 proto-oncogene HUGO:SPI1 hgnc_id:HGNC:11241 HGNC:11241 ENTREZ:6688 UNIPROT:P17947 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:20510871 SPI1 (PU.1) is a critical regulator of both conventional and plasmacytoid DC development. It is directly upregulates Flt3 gene activation. PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="SPI1"/> <bbox w="80.0" h="40.0" x="4125.0" y="1130.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2300_sa846" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: GATA binding protein 1 HUGO:GATA1 hgnc_id:HGNC:4170 HGNC:4170 ENTREZ:2623 UNIPROT:P15976 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10753833 GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GATA1"/> <bbox w="80.0" h="40.0" x="3985.0" y="970.0"/> </glyph> <glyph class="nucleic acid feature" id="s2301_sa852" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: GATA binding protein 1 HUGO:GATA1 hgnc_id:HGNC:4170 HGNC:4170 ENTREZ:2623 UNIPROT:P15976 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GATA1"/> <bbox w="90.0" h="25.0" x="3980.0" y="1047.5"/> <glyph class="unit of information" id="_2a9e6080-8eef-4455-b0d7-bab1aaa09bc1"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="4015.0" y="1042.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2302_sa853" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: GATA binding protein 1 HUGO:GATA1 hgnc_id:HGNC:4170 HGNC:4170 ENTREZ:2623 UNIPROT:P15976 Identifiers_end Maps_Modules_begin: MODULE:CORE_SIGNALING_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16418395 FLT3L induces PU.1 and STAT3 mRNA expression in DC progenitors and downregulates GATA1 mRNA expression. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="GATA1"/> <bbox w="70.0" h="25.0" x="3990.0" y="1107.5"/> </glyph> <glyph class="nucleic acid feature" id="s2303_sa854" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 1 receptor HUGO:CSF1R hgnc_id:HGNC:2433 HGNC:2433 ENTREZ:1436 UNIPROT:P07333 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16418395 FLT3 induces expression mRNAs of cytokine receptors G-CSFR, M-CSFR, and GM-CSFRa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1R"/> <bbox w="90.0" h="25.0" x="2165.0" y="1007.5"/> <glyph class="unit of information" id="_e4516c27-314a-476d-bd43-f0df91d7284f"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="2200.0" y="1002.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2304_sa855" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 1 receptor HUGO:CSF1R hgnc_id:HGNC:2433 HGNC:2433 ENTREZ:1436 UNIPROT:P07333 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16418395 FLT3 induces expression mRNAs of cytokine receptors G-CSFR, M-CSFR, and GM-CSFRa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF1R"/> <bbox w="70.0" h="25.0" x="2175.0" y="1077.5"/> </glyph> <glyph class="nucleic acid feature" id="s2305_sa856" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 2 receptor alpha subunit HUGO:CSF2RA hgnc_id:HGNC:2435 HGNC:2435 ENTREZ:1438 UNIPROT:P15509 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16418395 FLT3 induces expression mRNAs of cytokine receptors G-CSFR, M-CSFR, and GM-CSFRa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RA"/> <bbox w="70.0" h="25.0" x="3590.0" y="927.5"/> </glyph> <glyph class="nucleic acid feature" id="s2306_sa857" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: colony stimulating factor 2 receptor alpha subunit HUGO:CSF2RA hgnc_id:HGNC:2435 HGNC:2435 ENTREZ:1438 UNIPROT:P15509 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16418395 FLT3 induces expression mRNAs of cytokine receptors G-CSFR, M-CSFR, and GM-CSFRa References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RA"/> <bbox w="90.0" h="25.0" x="3580.0" y="847.5"/> <glyph class="unit of information" id="_32c38418-5533-4825-a15c-cd09924311b6"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3615.0" y="842.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2307_sa858" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: integrin subunit alpha X HUGO:ITGAX hgnc_id:HGNC:6152 HGNC:6152 ENTREZ:3687 UNIPROT:P20702 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:MARKERS_DC Maps_Modules_end References_begin: PMID:15573129 CD11c is a maker of myeloid DCs. PMID:8920882 FLT3 ligand upregulates surface expression of CD11c in DCs. 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For survival in vitro, myeloid DCs are dependent on GM-CSF, whereas pDCs are dependent on IL-3 and IFNA. PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL3RA"/> <bbox w="80.0" h="50.0" x="1965.0" y="995.0"/> <glyph class="unit of information" id="_7a970754-0328-48e5-b87d-281764412d7a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1982.5" y="990.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2310_sa862" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine receptor 5 (gene/pseudogene) HUGO:CCR5 hgnc_id:HGNC:1606 HGNC:1606 ENTREZ:1234 UNIPROT:P51681 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines CCL5(RANTES), CCL3(MIP-1α), and, especially, CCL4( MIP-1β). 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This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines CCL5(RANTES), CCL3(MIP-1α), and, especially, CCL4( MIP-1β). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCR5"/> <clone/> <bbox w="80.0" h="50.0" x="2685.0" y="455.0"/> <glyph class="unit of information" id="_c67b23bd-d672-4102-8ce5-30cb35a462d4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2702.5" y="450.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2311_sa863" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine receptor 5 (gene/pseudogene) HUGO:CCR5 hgnc_id:HGNC:1606 HGNC:1606 ENTREZ:1234 UNIPROT:P51681 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines CCL5(RANTES), CCL3(MIP-1α), and, especially, CCL4( MIP-1β). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCR5"/> <bbox w="80.0" h="50.0" x="2645.0" y="795.0"/> <glyph class="unit of information" id="_40e1929f-6436-45f1-9a6d-462d82007a5c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="2662.5" y="790.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2312_sa864"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 5 HUGO:CCL5 hgnc_id:HGNC:10632 HGNC:10632 ENTREZ:6352 UNIPROT:P13501 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines CCL5(RANTES), CCL3(MIP-1α), and, especially, CCL4( MIP-1β). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL5"/> <bbox w="80.0" h="40.0" x="2555.0" y="260.0"/> </glyph> <glyph class="macromolecule" id="s2313_sa865"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 4 HUGO:CCL4 hgnc_id:HGNC:10630 HGNC:10630 ENTREZ:6351 UNIPROT:P13236 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines CCL5(RANTES), CCL3(MIP-1α), and, especially, CCL4( MIP-1β). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL4"/> <bbox w="80.0" h="40.0" x="2555.0" y="200.0"/> </glyph> <glyph class="macromolecule" id="s2314_sa866"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 3 HUGO:CCL3 hgnc_id:HGNC:10627 HGNC:10627 ENTREZ:6348 UNIPROT:P10147 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines CCL5(RANTES), CCL3(MIP-1α), and, especially, CCL4( MIP-1β). References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL3"/> <bbox w="80.0" h="40.0" x="2555.0" y="320.0"/> </glyph> <glyph class="nucleic acid feature" id="s2315_sa868" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 19 HUGO:CCL19 hgnc_id:HGNC:10617 HGNC:10617 ENTREZ:6363 UNIPROT:Q99731 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL19"/> <bbox w="70.0" h="25.0" x="2680.0" y="1017.5"/> </glyph> <glyph class="nucleic acid feature" id="s2316_sa869" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 19 HUGO:CCL19 hgnc_id:HGNC:10617 HGNC:10617 ENTREZ:6363 UNIPROT:Q99731 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL19"/> <bbox w="90.0" h="25.0" x="2670.0" y="947.5"/> <glyph class="unit of information" id="_91c01337-bf05-478f-b8f9-9260f859dc79"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="2705.0" y="942.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2317_sa870" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 19 HUGO:CCL19 hgnc_id:HGNC:10617 HGNC:10617 ENTREZ:6363 UNIPROT:Q99731 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:17035340 The secretion of HMGB1 is required for the migration of maturing dendritic cells. myeloid DC, which rapidly secrete upon maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up-regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to migrate in response to chemokine receptor ligands. The events are apparently causally related: DC challenged with LPS in the presence of HMGB1-specific antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and to rearrange actin-rich structures. Moreover, DC matured in the presence of anti-HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the CXCR4 ligand CXCL12 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL19"/> <bbox w="80.0" h="40.0" x="2675.0" y="870.0"/> </glyph> <glyph class="macromolecule" id="s2318_sa871" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 18 HUGO:CCL18 hgnc_id:HGNC:10616 HGNC:10616 ENTREZ:6362 UNIPROT:P55774 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL18"/> <bbox w="80.0" h="40.0" x="5765.0" y="1880.0"/> </glyph> <glyph class="nucleic acid feature" id="s2319_sa872" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 18 HUGO:CCL18 hgnc_id:HGNC:10616 HGNC:10616 ENTREZ:6362 UNIPROT:P55774 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL18"/> <bbox w="90.0" h="25.0" x="5760.0" y="1807.5"/> <glyph class="unit of information" id="_73be548b-3889-49a7-9182-d20365f32b56"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5795.0" y="1802.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2320_sa873" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: C-C motif chemokine ligand 18 HUGO:CCL18 hgnc_id:HGNC:10616 HGNC:10616 ENTREZ:6362 UNIPROT:P55774 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:11698286 IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CCL18"/> <bbox w="70.0" h="25.0" x="5770.0" y="1717.5"/> </glyph> <glyph class="nucleic acid feature" id="s2321_sa874" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 10 HUGO:TNFSF10 hgnc_id:HGNC:11925 HGNC:11925 ENTREZ:8743 UNIPROT:P50591 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:10811870, PMID:17617740 I IFN induces TRAIL mRNA expression in DCs and enhances apoptosis of target tumor cells. Probabli via STAT1 and IFR1. (ChIP analyses demonstrated that IFNα induced direct, time-dependent binding of both transcription factors to the TRAIL promoter in model, but not dendritic cell line). PMID:17985330 IFN-β induces IRF1 expression, probably via STAT1in DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAIL*"/> <bbox w="70.0" h="25.0" x="3401.0" y="3077.5"/> </glyph> <glyph class="nucleic acid feature" id="s2322_sa875" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 10 HUGO:TNFSF10 hgnc_id:HGNC:11925 HGNC:11925 ENTREZ:8743 UNIPROT:P50591 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING MODULE:DC Maps_Modules_end References_begin: PMID:10811870 I IFN induces TRAIL mRNA expression in DCs and enhances apoptosis of target tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAIL*"/> <bbox w="90.0" h="25.0" x="3390.0" y="3137.5"/> <glyph class="unit of information" id="_e14337a7-1c2e-4109-a637-19072b8979c8"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3425.0" y="3132.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2324_sa876" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 10 HUGO:TNFSF10 hgnc_id:HGNC:11925 HGNC:11925 ENTREZ:8743 UNIPROT:P50591 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:23510023, PMID:23170255 TRAIL, FASL and TNF provides Dendritic cell tumor killing activity. PMID:11823516 Human immature dendritic cells express on their cell surface four different cytotoxic TNF family ligands: TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis inducing ligand; while cancer cells express the corresponding death receptors. Disruptions of interactions between the four ligands expressed on DCs and corresponding death-signaling receptors expressed on cancer cells using specific Abs or R:Fc fusion proteins block the cytotoxic activity of DCs directed against cancer cells. PMID:10811870 I IFN induces TRAIL mRNA expression in DCs and enhances apoptosis of target tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAIL*"/> <bbox w="80.0" h="40.0" x="3395.0" y="3200.0"/> </glyph> <glyph class="macromolecule" id="s2325_sa877" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon regulatory factor 1 HUGO:IRF1 hgnc_id:HGNC:6116 HGNC:6116 ENTREZ:3659 UNIPROT:P10914 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:10811870, PMID:17617740 I IFN induces TRAIL mRNA expression in DCs and enhances apoptosis of target tumor cells. Probabli via STAT1 and IFR1. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRF1"/> <bbox w="80.0" h="40.0" x="4015.0" y="1960.0"/> </glyph> <glyph class="nucleic acid feature" id="s2326_sa878" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon regulatory factor 1 HUGO:IRF1 hgnc_id:HGNC:6116 HGNC:6116 ENTREZ:3659 UNIPROT:P10914 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:10811870, PMID:17617740 I IFN induces TRAIL mRNA expression in DCs and enhances apoptosis of target tumor cells. Probabli via STAT1 and IFR1. PMID:11244049 IRF1 is a Stat1 target gene. PMID:17985330 IFN-β induces IRF1 expression, probably via STAT1in DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRF1"/> <bbox w="70.0" h="25.0" x="4020.0" y="1817.5"/> </glyph> <glyph class="nucleic acid feature" id="s2327_sa879" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interferon regulatory factor 1 HUGO:IRF1 hgnc_id:HGNC:6116 HGNC:6116 ENTREZ:3659 UNIPROT:P10914 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:CORE_SIGNALING_PATHWAYS Maps_Modules_end References_begin: PMID:10811870, PMID:17617740 I IFN induces TRAIL mRNA expression in DCs and enhances apoptosis of target tumor cells. Probabli via STAT1 and IFR1. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IRF1"/> <bbox w="90.0" h="25.0" x="4010.0" y="1897.5"/> <glyph class="unit of information" id="_c00bbd73-1f5c-48f2-a63c-9baf73002d8c"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="4045.0" y="1892.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2330_sa884" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD86 molecule HUGO:CD86 hgnc_id:HGNC:1705 HGNC:1705 ENTREZ:942 UNIPROT:P42081 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CHEKPOINTS Maps_Modules_end References_begin: PMID:15197224, PMID:7523569, PMID:9359474 The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. PMID:20805416 Expression of CD86, a critical costimulatory molecule for efficient T cell priming, is enhanced in activated mDCs during mTOR inhibition This phenotype was not observed in moDCs, in which surface expression of CD80 and CD86 was inhibited by rapamycin. PMID:11964292,PMID:14764699 IFNAR signaling upregulates surface expression of CD80, CD86, CD40.Probably via STAT1 PMID:22437870 CD80 and CD86 act lic coactivators of T-cells when they interact with CD28 and inhibit T-cells via interactions with CTLA4 PMID:10477595, PMID:8920882, PMID: 25215878 FLT3L induces Ag-presenting ability of Dcs. Probably via induction of surface expression of class II MHC and CD86. PMID:22076556, PMID:21220452, PMID:24218453 In immature DCs, internalization of MHC class II molecules from the plasma membrane may require the ubiquitin ligase MARCH1, which is controlled by interleukin-10 (IL-10). CD83 on mature DCs prevents this ubiquitylation of MHC class II molecules and thus stabilizes MHC class II molecules on the cell surface. Addidionally it prevents CD86 ubiquitinqtion. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD86"/> <bbox w="80.0" h="40.0" x="4505.0" y="3420.0"/> <glyph class="state variable" id="_08578f86-2d2a-425c-b34c-5f2e62b29e7a"> <state value="Ub" variable=""/> <bbox w="20.0" h="10.0" x="4495.0" y="3435.0"/> </glyph> <glyph class="unit of information" id="_407d4d5a-873b-4759-a556-dcd4adeffbee"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4522.5" y="3415.0"/> </glyph> </glyph> <glyph class="source and sink" id="s2340_sa889" compartmentRef="c1_ca1"> <label text="sa884_degraded"/> <bbox w="30.0" h="30.0" x="4530.0" y="3345.0"/> </glyph> <glyph class="macromolecule" id="s2341_sa890" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: membrane associated ring-CH-type finger 1 HUGO:MARCH1 hgnc_id:HGNC:26077 HGNC:26077 ENTREZ:55016 UNIPROT:Q8TCQ1 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MARCH1"/> <bbox w="80.0" h="40.0" x="4455.0" y="3540.0"/> </glyph> <glyph class="complex" id="s2342_csa129" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:MHC class II*:Tumor_antigen_fragment Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s17"/> <bbox w="120.0" h="140.0" x="4055.0" y="3380.0"/> <glyph class="macromolecule" id="s2344_sa891"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: major histocompatibility complex, class II, DM alpha HUGO:HLA-DMA hgnc_id:HGNC:4934 HGNC:4934 ENTREZ:3108 UNIPROT:P28067 major histocompatibility complex, class II, DM beta HUGO:HLA-DMB hgnc_id:HGNC:4935 HGNC:4935 ENTREZ:3109 UNIPROT:P28068 major histocompatibility complex, class II, DO alpha HUGO:HLA-DOA hgnc_id:HGNC:4936 HGNC:4936 ENTREZ:3111 UNIPROT:P06340 major histocompatibility complex, class II, DO beta HUGO:HLA-DOB hgnc_id:HGNC:4937 HGNC:4937 ENTREZ:3112 UNIPROT:P13765 major histocompatibility complex, class II, DP alpha 1 HUGO:HLA-DPA1 hgnc_id:HGNC:4938 HGNC:4938 ENTREZ:3113 UNIPROT:P20036 major histocompatibility complex, class II, DP beta 1 HUGO:HLA-DPB1 hgnc_id:HGNC:4940 HGNC:4940 ENTREZ:3115 UNIPROT:P04440 major histocompatibility complex, class II, DQ alpha 1 HUGO:HLA-DQA1 hgnc_id:HGNC:4942 HGNC:4942 ENTREZ:3117 UNIPROT:P01909 major histocompatibility complex, class II, DQ alpha 2 HUGO:HLA-DQA2 hgnc_id:HGNC:4943 HGNC:4943 ENTREZ:3118 UNIPROT:P01906 HLA-DQB1 antisense RNA 1 HUGO:HLA-DQB1-AS1 hgnc_id:HGNC:39762 HGNC:39762 ENTREZ:106480429 major histocompatibility complex, class II, DQ beta 2 HUGO:HLA-DQB2 hgnc_id:HGNC:4945 HGNC:4945 ENTREZ:3120 UNIPROT:P05538 major histocompatibility complex, class II, DR alpha HUGO:HLA-DRA hgnc_id:HGNC:4947 HGNC:4947 ENTREZ:3122 UNIPROT:P01903 major histocompatibility complex, class II, DR beta 1 HUGO:HLA-DRB1 hgnc_id:HGNC:4948 HGNC:4948 ENTREZ:3123 UNIPROT:P01911 major histocompatibility complex, class II, DR beta 3 HUGO:HLA-DRB3 hgnc_id:HGNC:4951 HGNC:4951 ENTREZ:3125 UNIPROT:P79483 major histocompatibility complex, class II, DR beta 4 HUGO:HLA-DRB4 hgnc_id:HGNC:4952 HGNC:4952 ENTREZ:3126 UNIPROT:P13762 major histocompatibility complex, class II, DR beta 5 HUGO:HLA-DRB5 hgnc_id:HGNC:4953 HGNC:4953 ENTREZ:3127 UNIPROT:Q30154 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:22076556, PMID:22076556, PMID:25720354 Like MHC class I molecules, class II molecules are also heterodimers, but in this case consist of two homogenous peptides, an α and β chain, both of which are encoded in the MHC. MHC class II molecules present antigen peptides to CD4+ T cells PMID:11702064 IL15 signaling upregulates surface expression of MHC class II PMID:22076556, PMID:21220452,PMID:24218453 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. PMID:19224634 STAT5 promotes expression of MHC class II transactivator protein (CIITA) and upregulates MHC class II expression downstream of CSF2. PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MHC class II*"/> <bbox w="80.0" h="40.0" x="4075.0" y="3450.0"/> <glyph class="state variable" id="_51e197be-cf8f-4ee8-8769-c99c14975544"> <state value="Ub" variable=""/> <bbox w="20.0" h="10.0" x="4065.0" y="3465.0"/> </glyph> <glyph class="unit of information" id="_be32baa2-2000-4bea-8831-a70331d35bf0"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4092.5" y="3445.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2343_sa892"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:11154916, PMID:11509172, PMID:22076556 Processed antigen peptide in lysosomes forms complex with MHC-class-II. formation and transport to the cell surface of MHC-class-II–peptide complexes is induced by maturation. Immature DCs in culture can take up antigen but do not present it efficiently to T cells. After detecting microbial products or proinflammatory cytokines, immature DCs transform into mature DCs, cells with a reduced capacity for antigen uptake but now with an exceptional capacity for T cell stimulation. PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. The resulting peptides are thought to be translocated into the lumen of the endoplasmic reticulum (ER) by specific transporters associated with antigen presentation (TAP), and loaded onto MHC class I molecules by a complex “loading machinery” (which includes tapasin, calreticulin and Erp57) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="Tumor_antigen_fragment"/> <bbox w="80.0" h="40.0" x="4075.0" y="3400.0"/> <glyph class="unit of information" id="_8678c094-da24-4e4e-8639-bafd0665cb95"> <label text="truncated"/> <bbox w="50.0" h="10.0" x="4090.0" y="3395.0"/> </glyph> </glyph> </glyph> <glyph class="source and sink" id="s2345_sa893" compartmentRef="c1_ca1"> <label text="csa129_degraded"/> <bbox w="30.0" h="30.0" x="4230.0" y="3395.0"/> </glyph> <glyph class="nucleic acid feature" id="s2347_sa896" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 CD1b molecule HUGO:CD1B hgnc_id:HGNC:1635 HGNC:1635 ENTREZ:910 UNIPROT:P29016 CD1c molecule HUGO:CD1C hgnc_id:HGNC:1636 HGNC:1636 ENTREZ:911 UNIPROT:P29017 CD1d molecule HUGO:CD1D hgnc_id:HGNC:1637 HGNC:1637 ENTREZ:912 UNIPROT:P15813 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:10837075, PMID:10358761, PMID:12391186 CD1 family as nonclassical, Ag-presenting molecules involved in regulation of T cell responses to microbial lipids and glycolipids-containing Ag. Both endogenous and exogenous lipids can be presented, and this pathway may contribute not only to microbial immunity but to autoimmunity and antitumor responses. In humans, four CD1 proteins (CD1a–d) are expressed by myeloid DCs, whereas in mice only CD1d has been identified References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1*"/> <bbox w="70.0" h="25.0" x="3400.0" y="1967.5"/> </glyph> <glyph class="nucleic acid feature" id="s2348_sa897" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 CD1b molecule HUGO:CD1B hgnc_id:HGNC:1635 HGNC:1635 ENTREZ:910 UNIPROT:P29016 CD1c molecule HUGO:CD1C hgnc_id:HGNC:1636 HGNC:1636 ENTREZ:911 UNIPROT:P29017 CD1d molecule HUGO:CD1D hgnc_id:HGNC:1637 HGNC:1637 ENTREZ:912 UNIPROT:P15813 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:10837075, PMID:10358761, PMID:12391186 CD1 family as nonclassical, Ag-presenting molecules involved in regulation of T cell responses to microbial lipids and glycolipids-containing Ag. Both endogenous and exogenous lipids can be presented, and this pathway may contribute not only to microbial immunity but to autoimmunity and antitumor responses. In humans, four CD1 proteins (CD1a–d) are expressed by myeloid DCs, whereas in mice only CD1d has been identified. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1*"/> <bbox w="90.0" h="25.0" x="3390.0" y="2027.5"/> <glyph class="unit of information" id="_a83837eb-7a53-40e6-82b1-1b8bc362569d"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3425.0" y="2022.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2262_sa898" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 CD1b molecule HUGO:CD1B hgnc_id:HGNC:1635 HGNC:1635 ENTREZ:910 UNIPROT:P29016 CD1c molecule HUGO:CD1C hgnc_id:HGNC:1636 HGNC:1636 ENTREZ:911 UNIPROT:P29017 CD1d molecule HUGO:CD1D hgnc_id:HGNC:1637 HGNC:1637 ENTREZ:912 UNIPROT:P15813 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:ANTIGEN_PRESENTATION Maps_Modules_end References_begin: PMID:10837075, PMID:10358761, PMID:12391186 CD1 family as nonclassical, Ag-presenting molecules involved in regulation of T cell responses to microbial lipids and glycolipids-containing Ag. Both endogenous and exogenous lipids can be presented, and this pathway may contribute not only to microbial immunity but to autoimmunity and antitumor responses. In humans, four CD1 proteins (CD1a–d) are expressed by myeloid DCs, whereas in mice only CD1d has been identified. CD1 proteins are functionally heterogeneous, and two subgroups can be identified. Subgroup I, including human CD1b–c, can present glycolipids to a large repertoire of T cells. Indeed, mycobacteria-specific, CD1b-restricted CD8+α/β TCR T cells have been demonstrated. Binding of the lipids to these CD1 molecules requires endosomal acidification. Subgroup II includes mouse and human CD1d and binds a limited set of Ags (α-galactosyloceramide) and activates a restricted set of T cells as well as NK T cells PMID:10190903 Alpha-galactosylceramide (alpha-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12-mediated antitumor activities. Production of IFN-gamma by NKT cells in response to alpha-GalCer required IL-12 produced by dendritic cells (DCs) and direct contact between NKT cells and DCs through CD40/CD40 ligand interactions. Moreover, alpha-GalCer strongly induced the expression of IL-12 receptor on NKT cells from wild-type but not CD1(-/-) or Valpha14(-/-) mice. PMID:15579430 Metastatic Melanoma Secreted IL-10 Down-Regulates CD1(CD1a, CD1b, CD1c, and CD1d) Molecules on Dendritic Cells in Metastatic Tumor Lesions. PMID:25582338 CD1a, which is involved in lipid Ag presentation, was significantly lower on imIL-15 DCs and mIL-15 DCs than on IL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1*"/> <bbox w="80.0" h="40.0" x="3395.0" y="2090.0"/> <glyph class="unit of information" id="_7e3b4d94-2761-4582-9ace-4b885af5dccb"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3412.5" y="2085.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2352_sa902" compartmentRef="c7_ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD74 molecule HUGO:CD74 hgnc_id:HGNC:1697 HGNC:1697 ENTREZ:972 UNIPROT:P04233 Identifiers_end Maps_Modules_begin: MODULE:ANTIGEN_PRESENTATION MODULE:DC Maps_Modules_end References_begin: PMID:16181339 Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD74"/> <bbox w="80.0" h="40.0" x="3955.0" y="2710.0"/> </glyph> <glyph class="macromolecule" id="s814_sa5" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: receptor interacting serine/threonine kinase 1 HUGO:RIPK1 hgnc_id:HGNC:10019 HGNC:10019 ENTREZ:8737 UNIPROT:Q13546 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:21232017, PMID:21133840, PMID:18641653 TNF induces TRADD-dependent and RIPK1-dependent recruitment of TRAF2 to TNFR1. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="RIPK1"/> <bbox w="80.0" h="40.0" x="4965.0" y="520.0"/> <glyph class="state variable" id="_b8e88060-bd0d-4e99-a5ff-614f9d9113dc"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="5040.0" y="535.4336"/> </glyph> </glyph> <glyph class="macromolecule" id="s813_sa6" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNFRSF1A associated via death domain HUGO:TRADD hgnc_id:HGNC:12030 HGNC:12030 ENTREZ:8717 UNIPROT:Q15628 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14730360 TRADD is an adaptor molecule important for transducing signals from TNFR1. After binding of TNF, TRADD is recruited to TNFR1 and interacts with the cytoplasmic death domain region of TNFR1 through homotypic interactions. The TNFR1-TRADD complex serves as scaffolding for the recruitment of other signaling molecules that mediate the downstream actions of TNF. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRADD"/> <bbox w="80.0" h="40.0" x="4965.0" y="480.0"/> </glyph> <glyph class="macromolecule" id="s809_sa10" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Fas associated via death domain HUGO:FADD hgnc_id:HGNC:3573 HGNC:3573 ENTREZ:8772 UNIPROT:Q13158 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FADD"/> <bbox w="80.0" h="40.0" x="4965.0" y="560.0"/> </glyph> <glyph class="complex" id="s2361_csa130" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL2:IL2RA:IL2RB:IL2RG:JAK1:JAK3 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2275"/> <bbox w="277.5" h="120.0" x="6926.25" y="1760.0"/> <glyph class="macromolecule" id="s2362_sa903"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit alpha HUGO:IL2RA hgnc_id:HGNC:6008 HGNC:6008 ENTREZ:3559 UNIPROT:P01589 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:10849428 IL-2 and IL-15 are able to induce the phosphorylation of ERK1/2. probably via PI3K pathway. MKK/ERK pathway is necessary for IL-2 to activate NK cells to express at least four known biological responses: LAK generation, IFN-gamma secretion, and IL2RA (CD25) and CLEC2C(CD69) expression. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RA"/> <bbox w="80.0" h="50.0" x="7023.75" y="1815.0"/> <glyph class="unit of information" id="_f29873bc-4fd0-44d2-8628-ee0f3f777109"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="7041.25" y="1810.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2363_sa904"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit beta HUGO:IL2RB hgnc_id:HGNC:6009 HGNC:6009 ENTREZ:3560 UNIPROT:P14784 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16212621 IL-2- and IL-15-induced phosphorylation of the IL-2RB chain in T cells. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RB"/> <bbox w="80.0" h="50.0" x="7113.75" y="1825.0"/> <glyph class="state variable" id="_a3ecc6a3-e9b1-4482-b554-9e6058002afb"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="7108.75" y="1845.0"/> </glyph> <glyph class="unit of information" id="_1515c8dd-4b81-4af6-bbbe-d8af7209d76a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="7131.25" y="1820.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2364_sa905"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 receptor subunit gamma HUGO:IL2RG hgnc_id:HGNC:6010 HGNC:6010 ENTREZ:3561 UNIPROT:P31785 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:16815076 IL-15 receptor complex contains IL15RA, IL2RG, IL2RB subunits. IL-15-mediated signaling results in the activation of Janus kinase (JAK), The IL-2RB chain recruits JAK1, whereas IL-2RG activates JAK3, , which in turn results in the phosphorylation and activation of STAT3 and STAT5, respectively. PMID:10820393, PMID:24829413 IL2 receptor is expressed in dendritic cells. The IL-2R is composed of three different subunits, IL-2R alpha (CD25), IL-2/15R beta (CD122) and gamma (CD131) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RG"/> <bbox w="80.0" h="50.0" x="7115.75" y="1765.0"/> <glyph class="unit of information" id="_d3cce981-35a0-4038-bfa6-0b7a989188b5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="7133.25" y="1760.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2365_sa906"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 2 HUGO:IL2 hgnc_id:HGNC:6001 HGNC:6001 ENTREZ:3558 UNIPROT:P60568 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24829413, PMID:15289500 IL-2 increases the ability of DCs to activate allogeneic CD8+ T Also dendritic cell-derived IL-2 for NK cell activation. PMID:24829413 IL-2 phosphorylates STAT5 to drive IFN-γ production and activation of human dendritic cells. PMID:15353479 Human and mouse DCs produce IL-2 downstream of IL15+CD40L signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2"/> <bbox w="80.0" h="40.0" x="7025.0" y="1770.0"/> </glyph> <glyph class="macromolecule" id="s2387_sa917"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 3 HUGO:JAK3 hgnc_id:HGNC:6193 HGNC:6193 ENTREZ:3718 UNIPROT:P52333 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:19759904 Jak3 is important for DC maturation, migration and function, through a CCR7-mediated signalling pathway. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK3"/> <bbox w="80.0" h="40.0" x="6935.0" y="1770.0"/> </glyph> <glyph class="macromolecule" id="s2388_sa918"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="6935.0" y="1820.0"/> <glyph class="state variable" id="_82af5213-5636-4376-8507-15bc031e7c3d"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6930.0" y="1835.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s2369_csa20" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IFNA:IFNAR1:IFNAR2 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:25333658 IFNAR−/− NK cells produce significantly less granzyme B than wild-type competitor NK cells PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1282"/> <bbox w="119.75" h="221.75" x="4105.125" y="379.125"/> <glyph class="macromolecule" id="s1285_sa120"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon alpha 2 HUGO:IFNA2 hgnc_id:HGNC:5423 HGNC:5423 ENTREZ:3440 UNIPROT:P01563 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15289500 Lytic function by NK cells and their ability to kill MHC-negative targets was regulated by type I IFNs produced by activated DCs. PMID:21930769, PMID:21930765 Type I interferon is selectively required by dendritic cells for immune rejection of tumors. Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. PMID:11698286 IFNA induces surface expression of CCR5 in Dcs. This higher expression of CCR5 was associated with a stronger chemotactic response of IFN-DCs to the β-chemokines RANTES, MIP-1α, and, especially, MIP-1β . Also IFNA induces mRNA expression both CCR7 and it's ligand CCL19 in Dcs and induces Dcs migration IFNA upregulates chemokine mRNA expression CCL18 (DC-DK1), CXCL10 (IP10) , PMID:11207245 IFNA induces IL10 production in Dcs (negative loop) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNA"/> <bbox w="80.0" h="40.0" x="4125.0" y="400.0"/> </glyph> <glyph class="macromolecule" id="s2370_sa121"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon alpha and beta receptor subunit 1 HUGO:IFNAR1 hgnc_id:HGNC:5432 HGNC:5432 ENTREZ:3454 UNIPROT:P17181 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:21930769 Type I interferon is selectively required by dendritic cells for immune rejection of tumors Sensitivity to type I IFN in innate immune cells is required for the generation of tumor-specific CTL. IFN-α/β signaling in DC acts via FNAR1 and STAT1. Type I IFN enhances the cross-presenting activity of CD8α+ lineage DCs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNAR1"/> <bbox w="80.0" h="50.0" x="4125.125" y="464.125"/> <glyph class="unit of information" id="_03ba6409-fb36-493f-b84e-0132ea01df8e"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4142.625" y="459.125"/> </glyph> </glyph> <glyph class="macromolecule" id="s2371_sa122"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interferon alpha and beta receptor subunit 2 HUGO:IFNAR2 hgnc_id:HGNC:5433 HGNC:5433 ENTREZ:3455 UNIPROT:P48551 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IFNAR2"/> <bbox w="80.0" h="50.0" x="4125.125" y="524.125"/> <glyph class="unit of information" id="_4a88ab5b-a9e5-469f-bd3e-b8c7823be046"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="4142.625" y="519.125"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2374_sa7" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF receptor associated factor 2 HUGO:TRAF2 hgnc_id:HGNC:12032 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:21232017, PMID:21133840, PMID:18641653 TNF induces TRADD-dependent and RIPK1-dependent recruitment of TRAF2 to TNFR1. TNFR2 interacts with TRAF2 and TRAF1. PMID:24378531 TNF via TNFR2 induces TRAF2 degradation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TRAF2"/> <bbox w="80.0" h="40.0" x="4965.0" y="440.0"/> <glyph class="state variable" id="_8593f55c-16eb-498d-bcd0-f3ce29f9a43b"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="5040.0" y="453.6673"/> </glyph> </glyph> <glyph class="complex" id="s2376_csa131" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CSF2RB:IL3RA Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2376"/> <bbox w="170.0" h="90.0" x="1830.0" y="685.0"/> <glyph class="macromolecule" id="s2377_sa908"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 3 receptor subunit alpha HUGO:IL3RA hgnc_id:HGNC:6012 HGNC:6012 ENTREZ:3563 UNIPROT:P26951 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:MARKERS_DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15573129, PMID:11698286 IL3RA is a maker of plasmacytoid DCs (pDCs). For survival in vitro, myeloid DCs are dependent on GM-CSF, whereas pDCs are dependent on IL-3 and IFNA. PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL3RA"/> <bbox w="80.0" h="50.0" x="1910.0" y="700.0"/> <glyph class="unit of information" id="_566f7606-fe83-4aaf-8917-7a2d68928693"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1927.5" y="695.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2378_sa909"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 2 receptor beta common subunit HUGO:CSF2RB hgnc_id:HGNC:2436 HGNC:2436 ENTREZ:1439 UNIPROT:P32927 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) ( References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RB"/> <bbox w="80.0" h="50.0" x="1830.0" y="700.0"/> <glyph class="unit of information" id="_dc2b4ac6-af70-4cdb-839d-c401ce4b4996"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1847.5" y="695.0"/> </glyph> </glyph> </glyph> <glyph class="complex" id="s2379_csa132" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:CSF2RB:IL3:IL3RA Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) ( References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s2376"/> <bbox w="175.0" h="125.0" x="1697.5" y="817.5"/> <glyph class="macromolecule" id="s2380_sa910"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 3 receptor subunit alpha HUGO:IL3RA hgnc_id:HGNC:6012 HGNC:6012 ENTREZ:3563 UNIPROT:P26951 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:MARKERS_DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15573129, PMID:11698286 IL3RA is a maker of plasmacytoid DCs (pDCs). For survival in vitro, myeloid DCs are dependent on GM-CSF, whereas pDCs are dependent on IL-3 and IFNA. PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL3RA"/> <bbox w="80.0" h="50.0" x="1782.5" y="867.5"/> <glyph class="unit of information" id="_de974e51-8a10-4ee1-b9a5-42de2c13c5ce"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1800.0" y="862.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2381_sa911"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: colony stimulating factor 2 receptor beta common subunit HUGO:CSF2RB hgnc_id:HGNC:2436 HGNC:2436 ENTREZ:1439 UNIPROT:P32927 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:12393492, PMID:22323450 CSF2 acts via heterodimer receptor contains CSF2RA and SSF2RB subunits anf use JAK2 kinase PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) ( References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CSF2RB"/> <bbox w="80.0" h="50.0" x="1702.5" y="867.5"/> <glyph class="unit of information" id="_732230ff-b497-49a7-b750-542a8d3344e5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1720.0" y="862.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2382_sa912"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 3 HUGO:IL3 hgnc_id:HGNC:6011 HGNC:6011 ENTREZ:3562 UNIPROT:P08700 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15549123 IL3 signaling is important for plasmacytoid DC which are expressing IL3RA. PMID:23762788 Tumor-infiltrating plasmacytoid dendritic cells (pDCs) have been associated with poor patient prognosis. PMID: 17200410, PMID:23125331, PMID:15034038 pDCs stimulated with IL-3 plus CD40L induce expression ICOS-L and OX40L. PMID:24778133, PMID:23026134 Expression ot ICOS-L and OX40L ligands by pDC promotes tumor progression by Promoting Th2 and Regulatory Immunity. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL3"/> <bbox w="80.0" h="40.0" x="1705.0" y="820.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2383_sa913" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 2 receptor subunit alpha HUGO:IL2RA hgnc_id:HGNC:6008 HGNC:6008 ENTREZ:3559 UNIPROT:P01589 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24829413 STAT5 is phosphorylated downstream IL2, It upregulate the promoter activity of both IL2RA and IFNG in dendritic cells downstream of IL2 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RA"/> <bbox w="70.0" h="25.0" x="6230.0" y="1567.5"/> </glyph> <glyph class="nucleic acid feature" id="s2384_sa914" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 2 receptor subunit alpha HUGO:IL2RA hgnc_id:HGNC:6008 HGNC:6008 ENTREZ:3559 UNIPROT:P01589 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24829413 STAT5 is phosphorylated downstream IL2, It upregulate the promoter activity of both IL2RA and IFNG in dendritic cells downstream of IL2 References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2RA"/> <bbox w="90.0" h="25.0" x="6220.0" y="1627.5"/> <glyph class="unit of information" id="_b2ea4ef6-3d4b-4a26-9c41-3d6102fe298e"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="6255.0" y="1622.5"/> </glyph> </glyph> <glyph class="macromolecule" id="s2385_sa915" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 5A HUGO:STAT5A hgnc_id:HGNC:11366 HGNC:11366 ENTREZ:6776 UNIPROT:P42229 signal transducer and activator of transcription 5B HUGO:STAT5B hgnc_id:HGNC:11367 HGNC:11367 ENTREZ:6777 UNIPROT:P51692 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24829413 STAT5 is phosphorylated downstream IL2, It upregulate the promoter activity of both IL2RA and IFNG in dendritic cells downstream of IL2 PMID:20231889 Stat5-Tg mice expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and has increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT5*"/> <bbox w="80.0" h="40.0" x="6175.0" y="1780.0"/> <glyph class="state variable" id="_f02fde3e-d215-4c08-af3f-5c3a3baded54"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="6170.0" y="1795.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2386_sa916" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: signal transducer and activator of transcription 5A HUGO:STAT5A hgnc_id:HGNC:11366 HGNC:11366 ENTREZ:6776 UNIPROT:P42229 signal transducer and activator of transcription 5B HUGO:STAT5B hgnc_id:HGNC:11367 HGNC:11367 ENTREZ:6777 UNIPROT:P51692 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24829413 STAT5 is phosphorylated downstream IL2, It upregulate the promoter activity of both IL2RA and IFNG in dendritic cells downstream of IL2 PMID:20231889 Stat5-Tg mice expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 and has increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="STAT5*"/> <bbox w="80.0" h="40.0" x="6175.0" y="1870.0"/> <glyph class="state variable" id="_8ea87a8d-39fe-478d-920b-222c0a60b61c"> <state value="P" variable=""/> <bbox w="15.0" h="10.0" x="6167.5" y="1885.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2389_sa919" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 2 HUGO:IL2 hgnc_id:HGNC:6001 HGNC:6001 ENTREZ:3558 UNIPROT:P60568 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:24829413, PMID:15289500 IL-2 increases the ability of DCs to activate allogeneic CD8+ T Also dendritic cell-derived IL-2 for NK cell activation. PMID:24829413 IL-2 phosphorylates STAT5 to drive IFN-γ production and activation of human dendritic cells. PMID:15353479 Human and mouse DCs produce IL-2 downstream of IL15+CD40L signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL2"/> <bbox w="80.0" h="40.0" x="5885.0" y="1870.0"/> </glyph> <glyph class="macromolecule" id="s2390_sa920" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inducible T-cell costimulator ligand HUGO:ICOSLG hgnc_id:HGNC:17087 HGNC:17087 ENTREZ:23308 UNIPROT:O75144 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:11007762 ICOSLG (B7RP1) is expressed on PB B cells and monocytes, and on PB monocyte-derived DC. It is the ligand to the co-stimulatory protein ICOS of T cells. PMID:17200410, PMID:23125331 pDCs stimulated with IL-3 plus CD40L gradually up-regulated CD80 and CD86 expression and became fully mature DCs within 6 d of culturing. In contrast, the up-regulation of ICOS-L was very strong and occurred very rapidly (reaching log 2–3 fluorescence intensity within the first 24 h of culturing. PMID:23026134 ICOS-Ligand Expression on Plasmacytoid Dendritic Cells Supports Breast Cancer Progression by Promoting the Accumulation of Immunosuppressive CD4+ T Cells References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ICOSLG"/> <bbox w="80.0" h="40.0" x="5405.0" y="3050.0"/> </glyph> <glyph class="nucleic acid feature" id="s2391_sa921" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 4 HUGO:TNFSF4 hgnc_id:HGNC:11934 HGNC:11934 ENTREZ:7292 UNIPROT:P23510 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:15034038 pDCs stimulated with IL-3 plus CD40L expressed OX40L (mRNA and protein), but produced almost no IFN-alpha in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="OX40L*"/> <bbox w="70.0" h="25.0" x="5390.0" y="2997.5"/> </glyph> <glyph class="nucleic acid feature" id="s2392_sa922" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: TNF superfamily member 4 HUGO:TNFSF4 hgnc_id:HGNC:11934 HGNC:11934 ENTREZ:7292 UNIPROT:P23510 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSTIMULATORY_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID:15034038 pDCs stimulated with IL-3 plus CD40L expressed OX40L (mRNA and protein), but produced almost no IFN-alpha in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="OX40L*"/> <bbox w="90.0" h="25.0" x="5280.0" y="3047.5"/> <glyph class="unit of information" id="_2a60c9a4-52d8-4975-bd7e-f987402ead94"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="5315.0" y="3042.5"/> </glyph> </glyph> <glyph class="complex" id="s1263_csa133" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL18:IL18R1:IL18RAP:MYD88 Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. The activated IL-1R–AcP complex recruits the serine/threonine kinase IL-1-receptor-associated kinase (IRAK) via the adaptor protein, MyD88. After IRAK is phosphorylated, it dissociates from the receptor complex and interacts with TNF-receptor-associated factor 6 (TRAF6), which then relays the signal via NF-κB-inducing kinase (NIK) to two I-κB kinases (IKK-1 and IKK-2) leading to NF-κB activation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1260"/> <bbox w="187.5" h="172.5" x="3191.25" y="453.75"/> <glyph class="macromolecule" id="s1261_sa923"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 18 receptor 1 HUGO:IL18R1 hgnc_id:HGNC:5988 HGNC:5988 ENTREZ:8809 UNIPROT:Q13478 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18R1"/> <bbox w="80.0" h="50.0" x="3198.75" y="511.25"/> <glyph class="unit of information" id="_3cabadec-82f5-4bb1-b6b1-9a50a9d0a29a"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3216.25" y="506.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s1262_sa924"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 1 receptor accessory protein HUGO:IL1RAP hgnc_id:HGNC:5995 HGNC:5995 ENTREZ:3556 UNIPROT:Q9NPH3 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18RAP"/> <bbox w="80.0" h="50.0" x="3288.75" y="511.25"/> <glyph class="unit of information" id="_b75bee8d-dd98-4bf7-8510-4baa26f5a30c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3306.25" y="506.25"/> </glyph> </glyph> <glyph class="macromolecule" id="s1266_sa925"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 18 HUGO:IL18 hgnc_id:HGNC:5986 HGNC:5986 ENTREZ:3606 UNIPROT:Q14116 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:9469432 IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells PMID:10679398 The role of IL-18 in innate immunity. PMID:15802534 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro-IL18 PMID:14504095, PMID:14662834 IL-18 induces chemotaxis of pDC. PMID:14662834 IL-18 had a direct migratory effect on MoDC as indicated by induction of filamentous actin polymerization and migration in Boyden chamber experiments (MoDC migrated toward an IL-18 gradient in Boyden chamber assays). In epidermal DC, IL-18 was also able to induce filamentous actin polymerization. Therefore,IL-18 might represent a novel mechanism to recruit DC to areas of inflammation. IL-18 up-regulated most strikingly the surface expression of CD54 (ICAM1) and induces F-actin polymerization PMID:11592085 ICAM-1 regulates the migration of dendritic cells into regional lymph nodes References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18"/> <bbox w="80.0" h="40.0" x="3198.75" y="466.25"/> </glyph> <glyph class="macromolecule" id="s1277_sa926"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: myeloid differentiation primary response 88 HUGO:MYD88 hgnc_id:HGNC:7562 HGNC:7562 ENTREZ:4615 UNIPROT:Q99836 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:14660645, PMID:16878026, PMID:23681101 The adaptor proteins MyD88 and TIRAP associate with TLR 2 and TLR 4 after receptor engagement. PMID:23811849 HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and iactivates TLR4/MyD88 pathway in dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. PMID:17704786 DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="MYD88"/> <bbox w="80.0" h="40.0" x="3198.75" y="566.25"/> </glyph> </glyph> <glyph class="complex" id="s1260_csa134" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:IL18R1:IL18RAP Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="s1260"/> <bbox w="180.0" h="100.0" x="3205.0" y="300.0"/> <glyph class="macromolecule" id="s1264_sa927"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 18 receptor 1 HUGO:IL18R1 hgnc_id:HGNC:5988 HGNC:5988 ENTREZ:8809 UNIPROT:Q13478 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18R1"/> <bbox w="80.0" h="50.0" x="3215.0" y="325.0"/> <glyph class="unit of information" id="_b506058e-0789-458a-83ed-90acd768ccc5"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3232.5" y="320.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2410_sa928"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: interleukin 1 receptor accessory protein HUGO:IL1RAP hgnc_id:HGNC:5995 HGNC:5995 ENTREZ:3556 UNIPROT:Q9NPH3 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18RAP"/> <bbox w="80.0" h="50.0" x="3300.0" y="325.0"/> <glyph class="unit of information" id="_51d5f810-48b8-4e9a-82fc-c7ae4cea5a48"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3317.5" y="320.0"/> </glyph> </glyph> </glyph> <glyph class="macromolecule" id="s2402_sa940" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 18 receptor 1 HUGO:IL18R1 hgnc_id:HGNC:5988 HGNC:5988 ENTREZ:8809 UNIPROT:Q13478 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18R1"/> <bbox w="80.0" h="50.0" x="3315.0" y="705.0"/> <glyph class="unit of information" id="_aa903ff3-8ac3-4d0b-b1dd-67010b258b31"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3332.5" y="700.0"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2405_sa943" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 18 receptor 1 HUGO:IL18R1 hgnc_id:HGNC:5988 HGNC:5988 ENTREZ:8809 UNIPROT:Q13478 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14662834 IL-18RA and IL-18RB mRNA expression is up-regulated by IFN-gamma in DC References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18R1"/> <bbox w="90.0" h="25.0" x="3310.0" y="797.5"/> <glyph class="unit of information" id="_9357d4ea-0f2b-4c4e-b3dc-1964e6254679"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3345.0" y="792.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2406_sa944" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 receptor accessory protein HUGO:IL1RAP hgnc_id:HGNC:5995 HGNC:5995 ENTREZ:3556 UNIPROT:Q9NPH3 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14662834 IL-18RA and IL-18RB mRNA expression is up-regulated by IFN-gamma in DC References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18RAP"/> <bbox w="70.0" h="25.0" x="3430.0" y="887.5"/> </glyph> <glyph class="nucleic acid feature" id="s2407_sa945" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 receptor accessory protein HUGO:IL1RAP hgnc_id:HGNC:5995 HGNC:5995 ENTREZ:3556 UNIPROT:Q9NPH3 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14662834 IL-18RA and IL-18RB mRNA expression is up-regulated by IFN-gamma in DC References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18RAP"/> <bbox w="90.0" h="25.0" x="3420.0" y="797.5"/> <glyph class="unit of information" id="_abb92d63-933a-42d2-98fb-f610c6b0773f"> <label text="RNA"/> <bbox w="20.0" h="10.0" x="3455.0" y="792.5"/> </glyph> </glyph> <glyph class="nucleic acid feature" id="s2404_sa942" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 18 receptor 1 HUGO:IL18R1 hgnc_id:HGNC:5988 HGNC:5988 ENTREZ:8809 UNIPROT:Q13478 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:14662834 IL-18RA and IL-18RB mRNA expression is up-regulated by IFN-gamma in DC References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18R1"/> <bbox w="70.0" h="25.0" x="3320.0" y="887.5"/> </glyph> <glyph class="macromolecule" id="s1265_sa941" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 1 receptor accessory protein HUGO:IL1RAP hgnc_id:HGNC:5995 HGNC:5995 ENTREZ:3556 UNIPROT:Q9NPH3 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:10679398 IL-18 receptor system consists of a ligand-binding subunit, IL-1Rrp and a signal transducing subunit, AcPL, analogous to the IL-1 receptor system. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18RAP"/> <bbox w="80.0" h="50.0" x="3425.0" y="715.0"/> <glyph class="unit of information" id="_945950fb-3a20-439d-a5da-0e50ed409d43"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3442.5" y="710.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2408_sa619" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: Janus kinase 1 HUGO:JAK1 hgnc_id:HGNC:6190 HGNC:6190 ENTREZ:3716 UNIPROT:P23458 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: ‭21115385, PMID:23894201 ‭JAK1 is a member of the Janus kinase family. ‭The binding of IL-10 to its receptor activates two members of the Janus kinase family: Jak1 (associated with the IL-1OR1 and Tyk2 (associated with the IL-10R2). But in DC Tyk2 has no influence on STAT3 activation. PMID:19833085 IFNG receptor is assosiated with kinases JAK1 and JAK2 PMID:15864272 I IFN receptor has a multichain structures, which are composed of at least two distinct subunits: IFNAR1 and IFNAR2. IFNAR1 subunit is constitutively associated with tyrosine kinase 2 (TYK2), whereas IFNAR2 is associated with JAK1. The initial step in both type-I- and type-II-IFN-mediated signalling is the activation of these receptor-associated JAKs , which occurs in response to a ligand-dependent rearrangement and dimerization of the receptor subunits, followed by autophosphorylation and activation of the associated JAKs which in turn regulate the phosphorylation and activation of STATs. PMID:12095053, PMID:8683106 IL2 receptor in DC acts probably via JAK1 and JAK3 (demonstrated for NK and T-cells only) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="JAK1"/> <bbox w="80.0" h="40.0" x="4865.0" y="520.0"/> <glyph class="state variable" id="_9bc7766e-bba4-4254-9d80-efb5489c836a"> <state value="" variable=""/> <bbox w="10.0" h="10.0" x="4860.0" y="535.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2409_sa881"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 18 HUGO:IL18 hgnc_id:HGNC:5986 HGNC:5986 ENTREZ:3606 UNIPROT:Q14116 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC MODULE:IMMUNOSTIMULATORY_CYTOKINES_PATHWAYS Maps_Modules_end References_begin: PMID:9469432 IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells PMID:10679398 The role of IL-18 in innate immunity. PMID:15802534 Exposure to HMGB1 triggers DCs to produce pro-IL-1β, and pro-IL18 PMID:14504095, PMID:14662834 IL-18 induces chemotaxis of pDC. PMID:14662834 IL-18 had a direct migratory effect on MoDC as indicated by induction of filamentous actin polymerization and migration in Boyden chamber experiments (MoDC migrated toward an IL-18 gradient in Boyden chamber assays). In epidermal DC, IL-18 was also able to induce filamentous actin polymerization. Therefore,IL-18 might represent a novel mechanism to recruit DC to areas of inflammation. IL-18 up-regulated most strikingly the surface expression of CD54 (ICAM1) and induces F-actin polymerization PMID:11592085 ICAM-1 regulates the migration of dendritic cells into regional lymph nodes References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL18"/> <bbox w="80.0" h="40.0" x="3390.0" y="150.0"/> </glyph> <glyph class="macromolecule" id="s2413_sa949" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: intercellular adhesion molecule 1 HUGO:ICAM1 hgnc_id:HGNC:5344 HGNC:5344 ENTREZ:3383 UNIPROT:P05362 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:14662834 IL-18 up-regulated most strikingly the surface expression of CD54 (ICAM1) and induces F-actin polymerization PMID:11592085 ICAM-1 regulates the migration of dendritic cells into regional PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 (ICAM1) and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ICAM1"/> <bbox w="80.0" h="50.0" x="3095.0" y="735.0"/> <glyph class="unit of information" id="_6c0c461f-4ecb-48ce-bd96-23a23c26150d"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3112.5" y="730.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s2414_sa948" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: intercellular adhesion molecule 1 HUGO:ICAM1 hgnc_id:HGNC:5344 HGNC:5344 ENTREZ:3383 UNIPROT:P05362 Identifiers_end Maps_Modules_begin: MODULE:RECRUITMENT_OF_IMMUNE_CELLS MODULE:DC Maps_Modules_end References_begin: PMID:14662834 IL-18 up-regulated most strikingly the surface expression of CD54 (ICAM1) and induces F-actin polymerization PMID:11592085 ICAM-1 regulates the migration of dendritic cells into regional PMID:20231889 Dcs Stat5-Tg mice are expressing ot surface high levels of MHC-II and costimulatory molecules such as CD80, CD86 and CD54 (ICAM1) and have increased level of I12 secretion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="ICAM1"/> <bbox w="80.0" h="50.0" x="3095.0" y="615.0"/> <glyph class="unit of information" id="_3069dc8b-3f44-4282-a0aa-3cc95a5a676c"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="3112.5" y="610.0"/> </glyph> </glyph> <glyph class="phenotype" id="s2166_sa722"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="TUMOR_CELL"/> <bbox w="240.0" h="85.0" x="3470.0" y="4362.5"/> </glyph> <glyph class="macromolecule" id="s4959_sa959" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: inducible T-cell costimulator ligand HUGO:ICOSLG hgnc_id:HGNC:17087 HGNC:17087 ENTREZ:23308 UNIPROT:O75144 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CHEKPOINTS MODULE:DC Maps_Modules_end References_begin: PMID: 17200410, PMID:23125331, PMID:15034038 pDCs stimulated with IL-3 plus CD40L induce production ICOS-L and expression of OX40L. PMID:24778133 Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="B7H2*"/> <bbox w="80.0" h="40.0" x="755.0" y="2780.0"/> </glyph> <glyph class="macromolecule" id="s557_sa410" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: hypoxia inducible factor 1 alpha subunit HUGO:HIF1A hgnc_id:HGNC:4910 HGNC:4910 ENTREZ:3091 UNIPROT:Q16665 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:RECRUITMENT_OF_IMMUNE_CELLS Maps_Modules_end References_begin: PMID:22539295 The chemokine receptor CCR7 was expressed at higher levels in wild-type DCs compared with HIF1α-deficient DCs. Hypoxia leads to increased migration of BMDCs to CCL19 in an HIF1α-dependent manner. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="HIF1A"/> <bbox w="80.0" h="40.0" x="2925.0" y="970.0"/> </glyph> <glyph class="macromolecule" id="s4960_sa513" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD1a molecule HUGO:CD1A hgnc_id:HGNC:1634 HGNC:1634 ENTREZ:909 UNIPROT:P06126 Identifiers_end Maps_Modules_begin: MODULE:MARKERS_DC MODULE:DC Maps_Modules_end References_begin: PMID:11238627 SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-α. PMID:11306493 IL4 signaling upregulates CD1a on cell surface of DC cells. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="CD1A"/> <bbox w="80.0" h="50.0" x="5745.0" y="2885.0"/> <glyph class="unit of information" id="_976055cc-9228-4184-86df-de37b4e73ab4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="5762.5" y="2880.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s3866_sa968" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: kinase insert domain receptor HUGO:KDR hgnc_id:HGNC:6307 HGNC:6307 ENTREZ:3791 UNIPROT:P35968 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:17086423 Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2 (KDR) VEGF treatment enhanced the phospho-Erk 1 and 2 via KDR. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="KDR"/> <bbox w="80.0" h="50.0" x="435.0" y="2195.0"/> <glyph class="unit of information" id="_ee97928a-4ec0-4029-851d-72c022d59ca9"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="452.5" y="2190.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s3913_sa969" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: fms related tyrosine kinase 1 HUGO:FLT1 hgnc_id:HGNC:3763 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:16002046, PMID:9570538 Inhibitory function of VEGF on DC function is most likely mediated by Flt-1. PMID:16002046 Id1−/− DCs did not respond to the VEGF stimulus because of defective Flt-1 signaling in these mutant mice. Thus, Flt-1 seems to be an important player in VEGF–DC interactions. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT1"/> <bbox w="80.0" h="50.0" x="545.0" y="2220.0"/> <glyph class="unit of information" id="_58eca103-ecc5-4770-9710-0a82fff70eb0"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="562.5" y="2215.0"/> </glyph> </glyph> <glyph class="complex" id="s5064_csa137" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:KDR:VEGFA Identifiers_end Maps_Modules_begin: MODULE:INPUT_INHIBITORS MODULE:IMMUNE_SUPPRESSION MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: MAP:DENDRITIC_CELL CASCADE:VEGFA PMID:17086423 Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2 (KDR) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="KDR:VEGFA"/> <bbox w="100.0" h="120.0" x="705.0" y="2105.0"/> <glyph class="macromolecule" id="s3910_sa970"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: kinase insert domain receptor HUGO:KDR hgnc_id:HGNC:6307 HGNC:6307 ENTREZ:3791 UNIPROT:P35968 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:17086423 Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2 (KDR) VEGF treatment enhanced the phospho-Erk 1 and 2 via KDR. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="KDR"/> <bbox w="80.0" h="50.0" x="715.0" y="2160.0"/> <glyph class="unit of information" id="_b354249a-8734-4588-a8e3-fdb04eb0cdf9"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="732.5" y="2155.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s3911_sa971"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: vascular endothelial growth factor A HUGO:VEGFA hgnc_id:HGNC:12680 HGNC:12680 ENTREZ:7422 UNIPROT:P15692 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15573129, PMID:8837607 Vascular endothelial growth factor (VEGF) was the first tumour-derived factor shown to inhibit DC differentiation. The involvement of VEGF in tumour-induced defects in DC differentiation was indicated by in vitro experiments in which neutralizing VEGF-specific antibody abrogated the negative effect of tumour-cell-conditioned medium on the differentiation of DCs from HPCs. (VEGF) inhibit the activation of NF-B by blocking IB phosphorylation55, 101, 102, possibly through activation of STAT3 (signal transducer and activator of transcription 3). Recent data have shown that STAT3 might also bind p65 subunits of NF-B, thereby directly inhibiting NF-B activity PMID:9570538 VEGF inhibits TNF-α inducible activation of NF-κB in HPC, resulting in inhibition of DC differentiation PMID:16002046 Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="VEGFA"/> <bbox w="80.0" h="40.0" x="715.0" y="2115.0"/> </glyph> </glyph> <glyph class="complex" id="s5063_csa138" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: NAME:FLT1:VEGFA Identifiers_end Maps_Modules_begin: MODULE:INPUT_INHIBITORS MODULE:IMMUNE_SUPPRESSION MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: MAP:DENDRITIC_CELL CASCADE:VEGFA PMID:16002046 Id1−/− DCs did not respond to the VEGF stimulus because of defective Flt-1 signaling in these mutant mice. Thus, Flt-1 seems to be an important player in VEGF–DC interactions. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT1:VEGFA"/> <bbox w="100.0" h="130.0" x="795.0" y="2250.0"/> <glyph class="macromolecule" id="s3915_sa972"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: fms related tyrosine kinase 1 HUGO:FLT1 hgnc_id:HGNC:3763 HGNC:3763 ENTREZ:2321 UNIPROT:P17948 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:16002046, PMID:9570538 Inhibitory function of VEGF on DC function is most likely mediated by Flt-1. PMID:16002046 Id1−/− DCs did not respond to the VEGF stimulus because of defective Flt-1 signaling in these mutant mice. Thus, Flt-1 seems to be an important player in VEGF–DC interactions. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="FLT1"/> <bbox w="80.0" h="50.0" x="805.0" y="2310.0"/> <glyph class="unit of information" id="_dd6f604c-2ede-4743-9fb3-4200285762d4"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="822.5" y="2305.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s4495_sa973"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body> Identifiers_begin: vascular endothelial growth factor A HUGO:VEGFA hgnc_id:HGNC:12680 HGNC:12680 ENTREZ:7422 UNIPROT:P15692 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15573129, PMID:8837607 Vascular endothelial growth factor (VEGF) was the first tumour-derived factor shown to inhibit DC differentiation. The involvement of VEGF in tumour-induced defects in DC differentiation was indicated by in vitro experiments in which neutralizing VEGF-specific antibody abrogated the negative effect of tumour-cell-conditioned medium on the differentiation of DCs from HPCs. (VEGF) inhibit the activation of NF-B by blocking IB phosphorylation55, 101, 102, possibly through activation of STAT3 (signal transducer and activator of transcription 3). Recent data have shown that STAT3 might also bind p65 subunits of NF-B, thereby directly inhibiting NF-B activity PMID:9570538 VEGF inhibits TNF-α inducible activation of NF-κB in HPC, resulting in inhibition of DC differentiation PMID:16002046 Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="VEGFA"/> <bbox w="80.0" h="40.0" x="805.0" y="2255.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s4962_sa859" compartmentRef="c2_ca2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 3 receptor subunit alpha HUGO:IL3RA hgnc_id:HGNC:6012 HGNC:6012 ENTREZ:3563 UNIPROT:P26951 Identifiers_end Maps_Modules_begin: MODULE:DC MODULE:MARKERS_DC MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS Maps_Modules_end References_begin: PMID:15573129, PMID:11698286 IL3RA is a maker of plasmacytoid DCs (pDCs). For survival in vitro, myeloid DCs are dependent on GM-CSF, whereas pDCs are dependent on IL-3 and IFNA. PMID:23046136 The receptor for IL-3 comprises the cytokine-specific α subunit IL3Rα and the βc subunit (CSF2RB) References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL3RA"/> <bbox w="80.0" h="50.0" x="1955.0" y="905.0"/> <glyph class="unit of information" id="_efad8b37-2895-4a8e-926d-5df263bae196"> <label text="receptor"/> <bbox w="45.0" h="10.0" x="1972.5" y="900.0"/> </glyph> </glyph> <glyph class="macromolecule" id="s4967_sa519"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 HUGO:IL6 hgnc_id:HGNC:6018 HGNC:6018 ENTREZ:3569 UNIPROT:P05231 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15573129, PMID:8837607, PMID:9845545 Macrophage colony-stimulating factor (M-CSF) and IL-6 have also been reported to be involved in the tumour-mediated regulation of DC differentiation. PMID:15356132 The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:11306493 The presence of high (>400 pg/ml) concentrations of IL-6 and M-CSF in tumor cell supernatant was strongly correlated with the inhibitory capacity of tumor cell medium on MO-DC differentiation PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6"/> <clone/> <bbox w="80.0" h="40.0" x="1305.0" y="3480.0"/> </glyph> <glyph class="macromolecule" id="s4967_sa585"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: interleukin 6 HUGO:IL6 hgnc_id:HGNC:6018 HGNC:6018 ENTREZ:3569 UNIPROT:P05231 Identifiers_end Maps_Modules_begin: MODULE:IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS MODULE:DC Maps_Modules_end References_begin: PMID:15573129, PMID:8837607, PMID:9845545 Macrophage colony-stimulating factor (M-CSF) and IL-6 have also been reported to be involved in the tumour-mediated regulation of DC differentiation. PMID:15356132 The activation of STAT3 by IL-6 was required for the suppression of LPS-induced DC maturation. In addition, STAT3 was required for the IL-6-mediated suppression of bone-marrow-derived DC activation and/or maturation PMID:11306493 The presence of high (>400 pg/ml) concentrations of IL-6 and M-CSF in tumor cell supernatant was strongly correlated with the inhibitory capacity of tumor cell medium on MO-DC differentiation PMID:25582338 mIL-15 DCs secreted markedly greater amounts of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, TNFα, TNFβ and IFN-γ, compared with mIL-4 DCs, suggesting that mIL-15 DCs are more proinflammatory than mIL-4 DCs. The IFN-γ, TNFα and IL-6 transcripts were consistently expressed at higher levels at 330-, 14- and 20-folds, respectively, in donor-matched mIL-15 DCs than mIL-4 DCs References_end Confidence_begin: Confidence_end </body> </html> </notes> <label text="IL6"/> <clone/> <bbox w="80.0" h="40.0" x="2275.0" y="280.0"/> </glyph> <glyph class="macromolecule" id="s2232_sa785" compartmentRef="c1_ca1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end ----- content merged by Celldesigner to SBGN-ML translation ------ Identifiers_begin: CD47 molecule HUGO:CD47 hgnc_id:HGNC:1682 HGNC:1682 ENTREZ:961 UNIPROT:Q08722 Identifiers_end Maps_Modules_begin: MODULE:TUMOR_RECOGNITION_TUMOR_KILLING Maps_Modules_end References_begin: PMID:11509594 CD47 binds SIRP-α on DC. SIRP-α engagement down-regulates DC function CD47-Fc potently suppressed IL-12 and TNF-α release by monocyte-derived DC stimulated by SAC. The inhibitory effect was dose dependent, and significant suppression was seen with as little as 10 ng/ml CD47-Fc (Fig. 5⇓B). Other cytokines, including IL-6 and IL-10, were also suppressed, CD47-Fc not only suppressed cytokine release by maturing DC, but also largely prevented DC phenotypic maturation. As indicated in Fig. 6⇓, CD83 and CD86 up-regulation were strongly reduced regardless of the stimulus used. For CD80, the inhibition was almost complete in response to CD40 signaling, moderate in response to SAC, and modest, but significant in response to LPS. CD40 expression was weakly up-regulated during DC maturation. In all three conditions, SIRP-α ligation by CD47-Fc abrogated the CD40 increase. Note only a slight reduction in HLA-DR expression. All together, these results demonstrate that engagement of SIRP-α largely inhibits DC maturation. PMID:10657674, PMID:10657674 CD47 is expresed on dendritic cells PMID:10657674, PMID:14568985 CD47 engagement by Thrombospondin-1 inhibits cytokine production and maturation of human dendritic cells. 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</notes> <bbox w="10.0" h="10.0" x="4360.0" y="790.0"/> <port id="pr_d9e3540a-7df1-4e80-a64c-1b0d4f57cfbc_p1" x="4365.0" y="780.0"/> <port id="pr_d9e3540a-7df1-4e80-a64c-1b0d4f57cfbc_p2" x="4365.0" y="810.0"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_02426e79-74d6-40c9-a0b2-f9b46e19e166"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4404.5" y="499.36667"/> <port id="pr_02426e79-74d6-40c9-a0b2-f9b46e19e166_p1" x="4394.5" y="504.36667"/> <port id="pr_02426e79-74d6-40c9-a0b2-f9b46e19e166_p2" x="4424.5" y="504.36667"/> </glyph> <glyph class="process" orientation="vertical" id="pr_39b12a39-0682-4b4c-917a-2531d544d613"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="1350.0" y="1945.0"/> <port id="pr_39b12a39-0682-4b4c-917a-2531d544d613_p1" x="1355.0" y="1935.0"/> <port id="pr_39b12a39-0682-4b4c-917a-2531d544d613_p2" x="1355.0" y="1965.0"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_603533a2-3e70-4649-b355-adaaa4cd7484"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:14607900 FNG inhibits IL10 signalind via STAT1. STAT1 overexpression prevents STAT3 homodimerization. References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="1408.875" y="1995.0"/> <port id="pr_603533a2-3e70-4649-b355-adaaa4cd7484_p1" x="1398.875" y="2000.0"/> <port id="pr_603533a2-3e70-4649-b355-adaaa4cd7484_p2" x="1428.875" y="2000.0"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_b77ea247-eedd-411f-9399-2adcea5c8f7d"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:15145317 The activated IKK complex, predominantly acting through IKKb in an IKKg-dependent manner, catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of IkBa), polyubiquitination (at sites equivalent to Lys21 and Lys22 of IkBa) and subsequent degradation by the 26S proteasome. The released NF-kB dimers (in this pathway, most commonly the p50– RelA dimer) translocate to the nucleus, bind DNA and activate gene transcription. PMID:17485448 IL10 Iinhibits IKBa‭ ‬phosphorylation and proteasomal degradation and prevents activation of downstream‭ ‬NFkB‭ ‬signaling. PMID:14660645, PMID:18264787, PMID:11460167 Activated TAK1 phosphorylates IKK-beta proteins leading to activation of NF-κB downstream of HMGB1.. References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4931.75" y="1260.25"/> <port id="pr_b77ea247-eedd-411f-9399-2adcea5c8f7d_p1" x="4951.75" y="1265.25"/> <port id="pr_b77ea247-eedd-411f-9399-2adcea5c8f7d_p2" x="4921.75" y="1265.25"/> </glyph> <glyph class="process" orientation="vertical" id="pr_8faae2b6-ff22-4b1f-8932-292c19fb7343"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:15145317 The activated IKK complex catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of IkBa), polyubiquitination (at sites equivalent to Lys21 and Lys22 of IkBa) and subsequent degradation by the 26S proteasome. The released NF-kB dimers (in this pathway, most commonly the p50– RelA dimer) translocate to the nucleus, bind DNA and activate gene transcription. References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4742.9966" y="1409.375"/> <port id="pr_8faae2b6-ff22-4b1f-8932-292c19fb7343_p1" x="4747.9966" y="1399.375"/> <port id="pr_8faae2b6-ff22-4b1f-8932-292c19fb7343_p2" x="4747.9966" y="1429.375"/> </glyph> <glyph class="process" orientation="vertical" id="pr_6d6c5238-e9aa-4a90-a7e5-6bad06bdbf14"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="5098.084" y="1351.375"/> <port id="pr_6d6c5238-e9aa-4a90-a7e5-6bad06bdbf14_p1" x="5103.084" y="1371.375"/> <port id="pr_6d6c5238-e9aa-4a90-a7e5-6bad06bdbf14_p2" x="5103.084" y="1341.375"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_bc47e523-3549-4a0d-8414-7d3142605afc"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via prevention of degradation of IkBa PMID:11438547, PMID:24378531 Both TNFR1 and TNFR2 signaling pathways induce classical NFkB activation via IKBa degradation. References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4946.75" y="1404.5"/> <port id="pr_bc47e523-3549-4a0d-8414-7d3142605afc_p1" x="4936.75" y="1409.5"/> <port id="pr_bc47e523-3549-4a0d-8414-7d3142605afc_p2" x="4966.75" y="1409.5"/> </glyph> <glyph class="process" orientation="vertical" id="pr_7f26058e-336b-4537-a87a-32441c1100c8"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:17404308 CSF1 induces acomulation of p50 homodimer and inhibition of p65/p50 NF-kB signaling References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4187.4004" y="1364.8125"/> <port id="pr_7f26058e-336b-4537-a87a-32441c1100c8_p1" x="4192.4004" y="1354.8125"/> <port id="pr_7f26058e-336b-4537-a87a-32441c1100c8_p2" x="4192.4004" y="1384.8125"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_8434e6eb-4c7e-4ebd-a39e-a898d8a7bcee"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:14660645, PMID:18264787, PMID:11460167 Activated TAK1 phosphorylates IKK-beta proteins leading to activation of NF-κB downstream of HMGB1. PMID:21232017, PMID:21133840, PMID:17301840 PMID:24958845, PMID:24699077 The LUBAC complex ubiquitinates NEMO, a subunit of the IKK complex downstream of TNF and upregulates IkBa degradetion. References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4891.75" y="1055.25"/> <port id="pr_8434e6eb-4c7e-4ebd-a39e-a898d8a7bcee_p1" x="4881.75" y="1060.25"/> <port id="pr_8434e6eb-4c7e-4ebd-a39e-a898d8a7bcee_p2" x="4911.75" y="1060.25"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_07dd5eeb-189e-4b69-85a0-76d912632575"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:17550372, PMID:9743347 IL13 inhibits NFκB activation via inhibition of p65 nuclear migration in inflammatory marophages PMID:14660645, PMID:15644117 p38 MAPK participates in HMGB1-induced NF-κB Activation PMID:14660645 HMGB1 induces nuclear NF-κB translocation and activation of NFkB signaling via TLR4 and TLR2. PMID:17404308 CSF2 induces RELA nuclear translocation and formation p65/p50 heterodimers provided induction of NFkB signaling. References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4455.75" y="1457.1018"/> <port id="pr_07dd5eeb-189e-4b69-85a0-76d912632575_p1" x="4445.75" y="1462.1018"/> <port id="pr_07dd5eeb-189e-4b69-85a0-76d912632575_p2" x="4475.75" y="1462.1018"/> </glyph> <glyph class="process" orientation="vertical" id="pr_8c349254-d3c7-433e-8b80-fdf59709092c"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:21115385,PMID:10433356 IL10‭ ‬acts via IL10‭ ‬receptor. IL10‭ ‬first binds to IL10RA The IL10/IL10R1A ‬interaction changes the cytokine conformation allowing the association of the IL10/IL10RA ‬complex with IL10RB. PMID:‭15833879 ‭Anti IL-10 receptor–specific antibody switched TAMs from an M2 to an M1 macrophage–like phenotype. 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DCs can also internalize the peptide loaded heat shock proteins gp96 and Hsp70 through presently unknown mechanisms References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="3487.5" y="3222.5"/> <port id="pr_0a65c60c-aba8-4165-bdc3-f9b50f4e5283_p1" x="3492.5" y="3242.5"/> <port id="pr_0a65c60c-aba8-4165-bdc3-f9b50f4e5283_p2" x="3492.5" y="3212.5"/> </glyph> <glyph class="process" orientation="vertical" id="pr_e502a2f0-f30d-48e8-9ca3-3b13f3752d33"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="2760.0" y="2045.0"/> <port id="pr_e502a2f0-f30d-48e8-9ca3-3b13f3752d33_p1" x="2765.0" y="2065.0"/> <port id="pr_e502a2f0-f30d-48e8-9ca3-3b13f3752d33_p2" x="2765.0" y="2035.0"/> </glyph> <glyph class="process" orientation="vertical" id="pr_a6034812-8a73-446a-ba51-313ffe1da917"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="4147.5557" y="3846.25"/> <port id="pr_a6034812-8a73-446a-ba51-313ffe1da917_p1" x="4152.5557" y="3836.25"/> <port id="pr_a6034812-8a73-446a-ba51-313ffe1da917_p2" x="4152.5557" y="3866.25"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_d220cf38-2fe9-4722-93a2-9b70b8086ed2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="3570.0" y="2385.0"/> <port id="pr_d220cf38-2fe9-4722-93a2-9b70b8086ed2_p1" x="3590.0" y="2390.0"/> <port id="pr_d220cf38-2fe9-4722-93a2-9b70b8086ed2_p2" x="3560.0" y="2390.0"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_2a191908-408a-496a-931b-cb51265eb8d6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After phagocytosis, antigens are exported into the cytosol and degraded by the proteasome4, 5, 6. 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References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="3442.888" y="2102.363"/> <port id="pr_e4c95616-6278-4a28-8b70-c3620e87eee2_p1" x="3462.888" y="2107.363"/> <port id="pr_e4c95616-6278-4a28-8b70-c3620e87eee2_p2" x="3432.888" y="2107.363"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_cdd4d55b-0b7c-4d6f-878b-bd3d6b5ebf62"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an adaptation of their endocytic and phagocytic pathways. After antigen export to the cytosol and degradation by the proteasome, peptides are translocated by TAP into the lumen of the same phagosomes, before loading on phagosomal MHC class I molecules. 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The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed, degraded proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface. 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This complex controls movement of MHC-II vesicles along the actin cytoskeleton in human dendritic cells (DCs). 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References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="2852.5" y="3105.0"/> <port id="pr_e6d7d580-840c-46c3-a7d8-577b71bd9043_p1" x="2872.5" y="3110.0"/> <port id="pr_e6d7d580-840c-46c3-a7d8-577b71bd9043_p2" x="2842.5" y="3110.0"/> </glyph> <glyph class="process" orientation="horizontal" id="pr_5ab9ff59-b09e-4c6d-a75f-6628ed86d9b6"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:22790179, PMID:14508489 The presentation of exogenous antigens on MHC class I molecules, known as cross-presentation, is essential for the initiation of CD8+ T cell responses. 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id="pr_1418df45-634f-4330-8dd7-99cf5b33f58b"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="3400.0" y="1115.0"/> <port id="pr_1418df45-634f-4330-8dd7-99cf5b33f58b_p1" x="3420.0" y="1120.0"/> <port id="pr_1418df45-634f-4330-8dd7-99cf5b33f58b_p2" x="3390.0" y="1120.0"/> </glyph> <glyph class="process" orientation="vertical" id="pr_766914b4-dc36-4127-8ccc-260c4e7ff4d2"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="5492.9756" y="1855.625"/> <port id="pr_766914b4-dc36-4127-8ccc-260c4e7ff4d2_p1" x="5497.9756" y="1845.625"/> <port id="pr_766914b4-dc36-4127-8ccc-260c4e7ff4d2_p2" x="5497.9756" y="1875.625"/> </glyph> <glyph class="process" orientation="vertical" id="pr_d3bc7c38-0247-439a-8c15-180df23910d1"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:17485448 Inhibition of‭ ‬NFkB signaling downstream of‭ ‬ABIN3‭ ‬ inhibits expression of‭ ‬IL8,‭ ‬IL6,‭ ‬TNF,‭ ‬IL12 PMID:16413922 NFKBID (IkBNS) inhibit late phase (after 3h) of expression of proinflanotory cytokines Il-12p40 (IL-12p40), Il-18 (IL-18) and Csf3 (G_CSF). PMID:16243976 IRF4 downregulates expression of TNFa, IL12p40, IL6 probably via inhibition of NF-kB and JNK signaling pathways. PMID:17404308 CSF1 downregulates TNF, IL-23p19, IL-12p40 expression probably via induction of acomulation of p50 homodimer and inhibition of p65/p50 NF-kB signaling. CSF2 upregulates expression of TNF, and have positive influence on IL12p70 (p40+p35), IL23 (p40+p19) expression, probably via induction rapid IkBa degradetion, RELA nuclear translocation and formation p65/p50 heterodimers provided induction of NFkB signaling. PMID:23390297 MIF inhitits expression of M1 markers such as IL12p40 References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="5493.25" y="1766.875"/> <port id="pr_d3bc7c38-0247-439a-8c15-180df23910d1_p1" x="5498.25" y="1756.875"/> <port id="pr_d3bc7c38-0247-439a-8c15-180df23910d1_p2" x="5498.25" y="1786.875"/> </glyph> <glyph class="process" orientation="vertical" id="pr_5b5bad75-5cd6-4a30-b584-2b2015530c4d"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="5595.0" y="1766.875"/> <port id="pr_5b5bad75-5cd6-4a30-b584-2b2015530c4d_p1" x="5600.0" y="1756.875"/> <port id="pr_5b5bad75-5cd6-4a30-b584-2b2015530c4d_p2" x="5600.0" y="1786.875"/> </glyph> <glyph class="process" orientation="vertical" id="pr_810a5bbd-5408-42ac-99db-22e52df7b2b0"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:17404308 CSF2 have positive influence on IL12p70 (p40+p35), IL23 (p40+p19) expression, probably via induction rapid IkBa degradetion, RELA nuclear translocation and formation p65/p50 heterodimers provided induction of NFkB signaling. 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xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: References_end Confidence_begin: Confidence_end </body> </html> </notes> <bbox w="10.0" h="10.0" x="6130.0" y="2050.0"/> <port id="pr_b1d38155-a255-47e4-a753-c133e6ac7db3_p1" x="6135.0" y="2040.0"/> <port id="pr_b1d38155-a255-47e4-a753-c133e6ac7db3_p2" x="6135.0" y="2070.0"/> </glyph> <glyph class="process" orientation="vertical" id="pr_7198ec02-7a2f-480c-8a41-a689a4849ca7"> <notes> <html xmlns="http://www.w3.org/1999/xhtml" xmlns:celldesigner="http://www.sbml.org/2001/ns/celldesigner" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <head> <title/> </head> <body>Identifiers_begin: Identifiers_end Maps_Modules_begin: Maps_Modules_end References_begin: PMID:11875494 IL10-induced p38 phosphorylation. PMID:20435894 SHIP inhibit MAPKp38 activation and prevent MKNK1 phosphorylation by inhibiting the p38MAPK pathway downstream of IL10. PMID:10925299 IL13 induces p38 MAPK phosphorilation and activation, p38 MAPK participates in arginase activation downstream of IL13. PMID:23508573 HMGB1 induces activation (phosphorylation) of p38 via TLR4. PMID:12811837, PMID:16713974 TLR signaling can induces STAT1 phosphorylation via p38 and potentiate IFNG signaling. PMID:16713974 TLR2 activates (induces phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages. This activation is inhibited by IFNG signaling. PMID:11438547, PMID:24378531 Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK. 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PMID:16127449 PPARG sumoilated by PIAS1/UbC9 prevents dissociation of the NCoR–HDAC3 complex fro promoters and transrepresses NF-kB dependent expression NOS2, Ccl3, Ccl7, Cxcl10. PMID:15644117, PMID:17260466 HMGB1 induces NO production probably via NFkB dependent upregulation of INOS expression. PMID:17689680 STAT1 binds to INOS promoter and induces INOS expression and NO production downstream of IFNG in murine macrophages. Acetylation inhibits STAT1 binding to promotor. PMID:11399519 STAT1, IRF1 and NF-kB interact with NOS2 promoter and cooperatively activate NOS2 expression in macrophages downstteam of IFNG. PMID:23390297 MIF inhitits expression of M1 markers such as NOS2 (INOS). PMID;PMID:20194441 HIF1 upregulates expression of INOS. 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