IL-17 R, also known as IL-17 RA, is a 120 kDa type I transmembrane glycoprotein protein that plays a central role in inflammatory responses (1-3). Mature mouse IL‑17 R consists of a 291 amino acid (aa) extracellular domain, a 21 aa transmembrane segment, and a 521 aa cytoplasmic domain (4). The cytoplasmic domain contains a region homologous to the TIR domain of the TLR/IL-1 R family (5). Mouse IL-17 R shares 84% and 72% aa sequence identity with rat and human IL-17 R, respectively. Within the extracellular domain, it shares 18%-25 % sequence identity with mouse IL-17 RB, C, D, and E. While the expression of IL-17 is restricted to activated T cells, IL-17 R exhibits a broad tissue distribution (4). Even in the absence of ligand, IL-17 R exists on the cell surface as a multimer (6). IL-17 R can bind IL-17 but must associate with IL-17 RC to transduce signals (7, 8). Interestingly, human IL-17 R does not appear to form productive complexes with mouse IL-17 RC (8). The IL-17 R can also signal in response to IL-17F (9). IL-17 R ligation promotes T cell activation and the production of IL-6, G-CSF, SCF, and multiple pro‑inflammatory chemokines (4, 7, 9, 10). IL-17A and IL-17F synergize with TNF-alpha in the induction of CXCL1, G-CSF, and IL-6 (9, 11). This effect requires the presence of both TNF RI and TNF RII (9). IL-17 interactions with IL-17 R also inhibit the TNF-alpha induced up-regulation of fibroblast CCL5 and VCAM-1 (11). CCL5 and VCAM-1 induced effects are differentially sensitive to blockade with IL-17 R specific antibodies, suggesting that IL-17 R triggers divergent intracellular signals (11). In vivo, IL‑17 R activity is important for increased generation of neutrophils and their recruitment to sites of inflammation (10, 12, 13). IL-17 R is required for host defense against microbial infection and for the progression of arthritis from inflammation to destructive joint erosion (10, 13).