Interleukin-22 receptor (IL-22R) (IL-22R)

The Interleukin-22 receptor (IL-22R) is a heterodimeric transmembrane protein complex composed of the Interleukin-22 receptor subunit alpha-1 (IL-22RA1) and the Interleukin-10 receptor subunit beta (IL-10RB) (UniProt: P59901, Q08334). While IL-10RB is ubiquitously expressed, IL-22RA1 expression is restricted to non-hematopoietic cells, particularly epithelial cells in the skin, gut, and lungs, as well as hepatocytes (PubMed: 21909091). Upon binding its ligand, IL-22, the receptor complex activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, primarily STAT3, to promote cell survival, proliferation, and the production of antimicrobial peptides (PubMed: 18391952). This signaling is essential for maintaining mucosal barrier integrity and promoting tissue repair following injury. However, chronic overactivation of the IL-22R is linked to inflammatory diseases like psoriasis and atopic dermatitis, and it may contribute to tumor progression in certain cancers (PubMed: 24011562). Therapeutic strategies include IL-22 agonists like Efmarodocokin alfa for treating tissue injury and IL-22 pathway inhibitors like Fezakinumab for autoimmune conditions (ClinicalTrials.gov: NCT02401594).

Other names

IL-22 receptor complexIL-22RA1/IL-10RB heterodimerInterleukin-22 receptor subunit alpha-1 and Interleukin-10 receptor subunit beta complexIL-22R1/IL-10R2 complex

Agonism of the IL-22 receptor complex to activate the JAK/STAT3 pathway for tissue repair and antimicrobial defense; Antagonism of the IL-22/IL-22R axis to inhibit pro-inflammatory signaling and epithelial hyperplasia.