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

The Interleukin-22 receptor complex is a heterodimeric signaling assembly consisting of two subunits: the high-affinity Interleukin-22 receptor subunit alpha-1 (IL-22RA1) and the accessory Interleukin-10 receptor subunit beta (IL-10RB) (Sabat et al., 2014, Nature Reviews Drug Discovery). A defining characteristic of this receptor complex is its restricted expression pattern; while the IL-10RB subunit is ubiquitous, the IL-22RA1 subunit is primarily found on non-hematopoietic cells, such as epithelial cells of the skin, gastrointestinal tract, and respiratory system (Ouyang & O'Garra, 2019, Nature Reviews Immunology). Upon binding of its ligand, IL-22, the complex activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, specifically STAT3, which triggers the expression of genes involved in cell survival, proliferation, and the production of antimicrobial peptides like defensins and S100 proteins (UniProt Q8N6P7). This signaling is crucial for maintaining mucosal barrier integrity and promoting tissue repair following injury or infection. In clinical practice, the IL-22 receptor complex is a target for treating chronic inflammatory diseases; for instance, neutralizing antibodies like Fezakinumab have been investigated for psoriasis and atopic dermatitis, while IL-22-Fc fusion proteins like Efmarodocokin alfa are being developed to promote intestinal healing in inflammatory bowel disease (ClinicalTrials.gov NCT02548637). However, because IL-22 signaling promotes epithelial cell growth, there are significant safety concerns regarding its potential to facilitate the progression of certain cancers, particularly colorectal and squamous cell carcinomas.

Other names

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

Interleukin-22 receptor agonist, Interleukin-22 neutralization