Pro inflammatory cytokine, IL-17 (IL-17A or CTLA-8) plays a central role in inflammation and autoimmunity. The IL17, like other cytokines is produce by activation of T cell receptor through CD3 cross linking (4). IL-17 is a crucial effector cytokine, whose production is specifically triggered by IL-23, and it has been shown to be an essential inflammatory mediator in other autoimmune diseases and inflammatory conditions. In human the co- stimulation of T cells thru CD28 several co-stimulatory molecules (ICOS, 4-1BB, CD40L) mildly enhance the IL17 expression where as IL23 profoundly enhance the CD3 induced IL17 expression. The IL-17 expression is also sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathway. IL17 signaling requires its binding to IL17 receptor, IL17 receptor is expression is widespread, the activity of IL17 is most commonly defined by its ability to induce the expression of inflammatory cytokines, chemokines and other mediators by stromal cells. In mouse genetically deficient in IL17RA, the IL17 signaling is poorly compensated by IL17RC suggesting the biological activity of IL17 is dependent on a heteromeric receptor complex composed of IL17RA and IL17RC (2). At least three types of IL17 receptors are cloned and characterized, IL17RA, IL17RB and IL17RC, IL17C is expressed in multiple spliced variant form (IL17RC1, ILRC2, and ILRC3). IL17RA deficient mice also showed high susceptibility and recovery after infusion of IL17A to hemopieotic cytotoxicity to gamma radiation suggesting involvement of IL17R dependent inducible mechanism that is required for recovery of granulopoiesis after radiation injury (3). IL17R is also involvement in allograft rejection and Intragraft IL-17 inhibition may be useful as an adjuvant therapy to systemic immunosuppression in tissue transplantation. www. The predicted IL17RA receptor (866 aa) is a ubiquitous membrane glycoprotein that binds with low affinity to IL17A suggesting that additional component are involved in IL17-induced signaling. Like other cytokines receptors, IL17RA also has multimeric tructure. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases including rheumatoid arthritis. The IL17RA has at least 3 TMD that anchor the protein to the cell membrane with a large intrcyctoplasmic domain where protein and signaling molecules interact with the receptor complex.
Alternate names: CDw217, IL-17 receptor, IL17R, Interleukin-17 receptor A