Interleukin-17 receptor subunit alpha (IL-17RA)

Interleukin-17 receptor subunit alpha (IL-17RA) is a ubiquitously expressed type I transmembrane glycoprotein that serves as a critical component of several heterodimeric receptor complexes within the IL-17 family [1, 5, 10]. It primarily pairs with IL-17RC to mediate signaling for IL-17A and IL-17F, but also associates with IL-17RB and IL-17RE to transduce signals from IL-17E (IL-25) and IL-17C, respectively [10, 12]. Upon ligand binding, IL-17RA recruits the adaptor protein Act1 via its cytoplasmic SEFIR domain, triggering downstream pathways such as NF-κB and MAPK that drive the production of proinflammatory cytokines, chemokines, and antimicrobial peptides [1, 13]. This signaling is essential for host defense against extracellular bacteria and fungi but, when dysregulated, plays a central role in the pathogenesis of chronic inflammatory and autoimmune diseases like psoriasis and psoriatic arthritis [1, 5, 15]. Therapeutically, IL-17RA is a major target for monoclonal antibodies, most notably brodalumab, which acts as a direct antagonist by blocking the receptor's extracellular domain [1, 12]. Unlike inhibitors that target specific ligands, blocking IL-17RA provides a broader inhibitory effect by neutralizing multiple IL-17 isoforms that share this subunit [1, 10]. While highly effective in treating moderate-to-severe plaque psoriasis, targeting this receptor carries risks such as increased susceptibility to mucocutaneous candidiasis and specific safety warnings regarding suicidal ideation [9, 16, 17].

Other names

IL17RACD217IL-17RIL-17 receptor ACDw217

Receptor antagonist that binds to the extracellular domain of IL-17RA, preventing the binding of multiple IL-17 family cytokines (IL-17A, IL-17F, IL-17A/F, IL-17C, and IL-17E) and inhibiting downstream proinflammatory signaling.