The IL17RA receptor protein also binds IL-17A and IL-17F homodimers as part of a heterodimeric complex with IL17RC. The receptor protein binds to IL-17A with higher affinity than to IL-17F. Cytokine binding triggers interaction of the complex with the TRAF3IP2 adaptor, leading to TRAF6-mediated activation of the NF-kappaB and MAP kinase signaling pathways. This ultimately leads to transcriptional activation of cytokines, chemokines, antimicrobial peptides, and matrix metalloproteinases, resulting in a strong immune response.
This interleukin response pathway is involved in antimicrobial host defense, primarily by promoting the activation and recruitment of neutrophils to sites of infection to destroy extracellular bacteria and fungi. In secondary lymphoid organs, it contributes to the formation of germinal centers by regulating the chemotactic response of B cells to CXCL12 and CXCL13, promoting retention of B cells within germinal centers, somatic hypermutation rate of B cells, and selection toward plasma cells. Furthermore, the IL-17RA/IL-17A/F/C complex plays a role in maintaining the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting microbial invasion through epithelial barriers .It is involved in antiviral host defense through several mechanisms.
Interleukin-17 receptor A is a receptor for the SARS coronavirus-2/SARS-CoV-2 viral protein ORF8, which leads to activation of the IL-17 pathway and increased secretion of pro-inflammatory factors through activation of the NF-kappa-B pathway.