Identifiers
HUGO:LTF
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / RECRUITMENT_OF_IMMUNE_CELLS
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
References
CASCADE:LTF
NEUTROPHIL
DENDRITIC_CELL
CASCADE:TLR2_4
Gregory and colleagues have made an interesting observation that apoptotic cell supernatants also contain keep-out signals for neutrophils (Bournazou et al., 2009). Specifically, they identified that lactoferrin is released from apoptotic cells (in a caspase-dependent process) and that lactoferrin can act as a potent stop signal for neutrophil migration toward many other chemokines.
PMID:18364398
Lactoferrin (LF) is an important protein component of the innate immune system that is broadly distributed within the body fluids. LF is endowed with multiple biological activities. 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 microg/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-gamma in the presence of allogeneic human T cells. TLF-matured DCs are able to prime naive T cells to respond to KLH antigen and display a significantly increased capacity to present Flu-MA(58-66) peptide to HLA-A2-matched T cells. These data suggest that a key immunomodulatory function that may be mediated by TLF is to link the innate with adaptive immunity through DC maturation.
PMID:24088817
Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll-like receptors 2 and 4