IL-17A

Alias: Interleukin-17A, CTLA-8, IL-17

Interleukin-17A (IL-17A) is the prototypic member of the IL-17 family of cytokines. IL-17A plays a critical role in host defense and inflammation. IL-17A expression is most often associated with the T helper 17 (TH17) subset of CD4+ T cells, but has also been observed in CD8+ T cells, neutrophils, and γδ T cells upon stimulation with IL-1 and IL-23. IL-17A is most similarly related to IL-17F with which it shares 50% sequence homology. Both IL-17A and IL-17F exist as either biologically active homodimers (IL-17AA and IL-17FF) or biologically active heterodimers (IL-17AF). All three protein complexes are currently believed to signal through the same receptor complex (IL-17R) composed of the subunits IL-17RA and IL-17RC (IL-17RL), though they appear to have different biological functions. One of the principle IL-17 functions appears to be the regulation of local tissue inflammation via the coordinated expression of various cytokines and chemokines that include IL-1, IL-6, IL-8, GM-CSF, G-CSF, TNF, CXCL1, MCP-1, MIP-2, MCP-3, and MIP-3α. Upon ligand/receptor interaction, IL-17A induces these inflammatory cytokine production in epithelial cells, endothelial cells, and fibroblasts through the NFκB and MAPK family pathways that results in the activation of many of the AP-1 proteins. IL-17 has become an important target for drug discovery for the treatment of various forms of autoimmunity and inflammatory diseases such as asthma, rheumatoid arthritis, multiple sclerosis, psoriasis, transplant rejection, and inflammatory bowel disease (IBD).