IL10RA

Interleukin 10 receptor subunit alpha (IL10RA), also known as CDW210A or IL-10R1, is a transmembrane glycoprotein critical for mediating the anti-inflammatory effects of interleukin-10 (IL-10). It forms a heterodimeric receptor complex with IL10RB, enabling ligand binding and subsequent activation of JAK1 and TYK2 kinases. This triggers phosphorylation of STAT3, which translocates to the nucleus to suppress pro-inflammatory cytokine production and promote immune tolerance. Key pathways influenced include the JAK-STAT signaling cascade, particularly STAT3-mediated transcriptional regulation, and pathways modulating macrophage polarization and T-cell anergy.
Mutations in IL10RA are linked to severe early-onset inflammatory bowel disease (IBD), particularly infantile IBD and very early-onset IBD (VEO-IBD), due to defective immune regulation. Dysregulated IL10RA signaling is also implicated in autoimmune disorders and chronic inflammation. Therapeutic strategies targeting this pathway focus on recombinant IL-10 analogs (e.g., PEGylated IL-10) and small-molecule agonists to restore anti-inflammatory signaling. Clinical trials for IL-10 pathway modulators in IBD and psoriasis are ongoing, while JAK inhibitors like tofacitinib indirectly influence downstream STAT3 activity, offering broader immunomodulatory applications.