Interleukin-22 receptor subunit alpha-1 (IL22RA1) (IL22RA1)

Interleukin-22 receptor subunit alpha-1 (IL22RA1) is a high-affinity subunit of the heterodimeric receptor for interleukin-22 (IL-22), primarily expressed on non-immune cells such as epithelial cells in the skin, gut, and lungs, as well as hepatocytes (UniProt Q8N6P7). It forms a functional signaling complex with the shared IL10RB subunit to activate the JAK-STAT pathway, particularly STAT3, which regulates genes involved in cell survival, proliferation, and the production of antimicrobial peptides (NIH: PMC7311387). IL22RA1 also serves as a receptor for IL-20 and IL-24 when paired with IL20RB, expanding its role in cytokine signaling (GeneCards). While essential for maintaining epithelial barrier integrity and host defense against pathogens, dysregulated IL22RA1 signaling is implicated in the pathogenesis of chronic inflammatory diseases like psoriasis and inflammatory bowel disease (PubMed: 11035029). Furthermore, its overexpression is associated with poor prognosis in several cancers, including pancreatic and lung cancer, where it may promote tumor cell survival (NIH: PMC7311387). Therapeutic development focuses on IL-22 agonists, such as Efmarodocokin alfa, to promote tissue healing in conditions like alcoholic hepatitis and IBD (Cytoki Pharma). Conversely, IL-22R antagonists are being explored to treat autoimmune disorders characterized by excessive IL-22 activity (PubMed: 39354046).

Other names

IL-22R-alpha-1IL-22R1CRF2-9ZcytoR11Cytokine receptor class-II member 9Cytokine receptor family 2 member 9

Agonism of the IL-22 receptor complex (IL22RA1/IL10RB) to activate the JAK1/TYK2-STAT3 signaling pathway, promoting epithelial cell proliferation and tissue repair (UniProt Q8N6P7, NIH: PMC7311387). Antagonism of IL22RA1 to block IL-22-mediated pro-inflammatory signaling in conditions like psoriasis and IBD (PubMed: 39354046).