IL10RA

IL10RA, or Interleukin-10 receptor subunit alpha, is a protein encoded by the IL10RA gene in humans. It forms the alpha chain of the interleukin-10 receptor, which, together with the IL-10 receptor beta chain (IL10RB), constitutes the receptor for the anti-inflammatory cytokine IL-10. The receptor is expressed on various immune cells, including macrophages and dendritic cells, as well as on some epithelial cells.

Functionally, IL-10 binding promotes the assembly of the IL-10 receptor complex and activates intracellular signaling through the JAK-STAT pathway, primarily via JAK1 and TYK2, leading to phosphorylation and activation of STAT3. Activated STAT3 drives transcription of anti-inflammatory genes and suppresses pro-inflammatory cytokine production, NF-κB activity, and antigen presentation. This signaling pathway plays a key role in limiting excessive immune responses and maintaining intestinal and tissue homeostasis.

Clinical significance is most prominent in the context of genetic defects. Biallelic mutations in IL10RA cause autosomal recessive deficiencies in IL-10 signaling, often presenting as early-onset inflammatory bowel disease with severe colitis and perianal disease in infancy, and can be associated with recurrent infections and immune dysregulation. Similar disease phenotypes can occur with mutations in IL10RB or IL10, reflecting the importance of intact IL-10 signaling for immune regulation.

Management of IL10RA-related disorders has included supportive care and immunomodulatory therapies, with hematopoietic stem cell transplantation providing potential disease control in some patients. Ongoing research continues to define the full spectrum of IL10RA-related pathologies and to explore targeted approaches to restore or bypass defective signaling.