Interleukin-17A (IL-17A), also known as CTLA-8, is a 15-20 kDa glycosylated cytokine that plays an important role in anti-microbial and chronic inflammation. The six IL-17 cytokines (IL-17A-F)are encoded by separate genes but adopt a conserved cystine knot fold. Mature rat IL-17A shares 60% and 89% amino acid sequence identity with human and mouse IL-17A, respectively. IL-17A is secreted by Th17 cells, gamma /δ T cells, iNKT cells, NK cells, LTi cells, neutrophils, and intestinal Paneth cells. It forms disulfide-linked homodimers as well as disulfide-linked heterodimers with IL-17F. IL-17A exerts its effects through the transmembrane IL-17RA in complex with IL-17RC or IL-17RD. Both IL-17RA and IL-17RC are required for responsiveness to heterodimeric IL-17A/F. IL-17A promotes protective mucosal and epidermal inflammation in response to microbial infection. It induces chemokine production, neutrophil influx, and the production of antibacterial peptides. IL-17A/F likewise induces neutrophil migration, but IL-17F does not. IL-17A additionally enhances the production of inflammatory mediators by rheumatoid synovial fibroblasts and contributes to TNF-alpha induced shock. In contrast, it can protect against the progression of colitis by limiting chronic inflammation. IL-17A encourages the formation of autoreactive germinal centers and exacerbates the onset and progression of experimental models of autoimmunity. IL-17A has been shown to exert either tumorigenic or anti-tumor effects.
