IL10R1

IL-10 receptor 1, also known as IL-10R1 or IL10RA, is a transmembrane protein that serves as the alpha chain of the interleukin-10 receptor. It belongs to the class II cytokine receptor family. The IL-10 receptor is a heterotetramer composed of two IL-10R1 subunits and two IL-10R2 subunits; signaling is initiated when IL-10 binds to IL-10R1 and recruits IL-10R2. The IL10RA gene encodes IL-10R1 in humans.

Structure and expression: IL-10R1 contains an extracellular cytokine-binding domain, a single transmembrane helix, and a cytoplasmic tail that associates with the JAK-STAT signaling machinery. It is broadly expressed on immune cells such as monocytes, macrophages, dendritic cells, as well as on certain epithelial and stromal cells.

Signaling: Upon IL-10 binding to IL-10R1, IL-10R2 is recruited to form a signaling complex. The receptor-associated kinases JAK1 and TYK2 become activated, leading to phosphorylation of STAT3 (and to a lesser extent STAT1/STAT5). Phosphorylated STATs dimerize and translocate to the nucleus, promoting transcription of anti-inflammatory genes. Negative regulation by SOCS proteins provides feedback control.

Biological role: The IL-10/IL-10R1/IL-10R2 axis mediates anti-inflammatory responses, suppressing proinflammatory cytokine production and limiting antigen presentation. It contributes to tissue homeostasis in the gut and other tissues and modulates immune responses during infection and inflammation.

Clinical significance: Loss-of-function mutations in IL10RA cause autosomal recessive, early-onset inflammatory bowel disease and severe infantile enterocolitis. Such IL-10R deficiencies highlight the importance of IL-10 signaling in intestinal homeostasis and may require hematopoietic stem cell transplantation in affected patients. Mouse models lacking IL-10R1 display spontaneous colitis, illustrating the receptor's role in regulating intestinal inflammation.