IL17RA

Interleukin-17 receptor A (IL-17RA) is a transmembrane receptor subunit of the interleukin-17 receptor family. It forms signaling complexes with other IL-17 receptor subunits and mediates responses to several IL-17 family cytokines. In particular, IL-17A and IL-17F signal through a heteromeric complex of IL-17RA and IL-17RC, whereas other IL-17 family members use different subunit combinations.

IL-17RA contains an extracellular ligand-binding domain and a cytoplasmic SEFIR domain that recruits the adaptor protein Act1 to propagate signaling. Ligand binding activates NF-κB and MAPK pathways, leading to transcription of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. IL-17RA is broadly expressed, with high levels on epithelial and endothelial cells and various leukocytes; expression can be upregulated during inflammation.

Physiological function includes promoting host defense at barrier surfaces, notably against fungi such as Candida and certain bacteria. In disease, IL-17RA–mediated signaling drives tissue inflammation and neutrophil recruitment and is implicated in autoimmune conditions such as psoriasis, psoriatic arthritis, and inflammatory bowel disease.

Therapeutically, blockade of IL-17 signaling can reduce disease activity in several inflammatory diseases. Drugs targeting IL-17A (e.g., secukinumab, ixekizumab) or IL-17RA (e.g., brodalumab) are approved for psoriasis and related conditions. Inhibition of this pathway raises the risk of mucocutaneous candidiasis and other infections. Rare IL17RA deficiencies in humans cause susceptibility to chronic mucocutaneous candidiasis and immunodeficiency features.