Interleukin-10 receptor (IL-10R) (IL-10R)

The Interleukin-10 receptor (IL-10R) is a transmembrane heterotetrameric complex composed of two IL-10RA (IL-10R1) and two IL-10RB (IL-10R2) subunits (UniProt P40189, Q08334). It serves as the primary mediator for the potent anti-inflammatory effects of the cytokine IL-10 by activating the JAK/STAT signaling pathway, specifically involving JAK1, Tyk2, and STAT3 (PubMed: 24591369). This signaling cascade suppresses the production of pro-inflammatory cytokines such as TNF-alpha and IL-6 in macrophages and dendritic cells (NCBI: NBK26887). In clinical contexts, the IL-10R is a target for treating chronic inflammatory conditions; for instance, loss-of-function mutations in IL-10R subunits are linked to severe, early-onset inflammatory bowel disease (PubMed: 19892438). In oncology, pegylated recombinant IL-10 (Pegilodecakin) has been investigated to stimulate CD8+ T-cell mediated anti-tumor responses through the IL-10R complex (ClinicalTrials.gov: NCT02009449). The receptor's dual role in maintaining immune homeostasis and influencing the tumor microenvironment makes it a critical focus for both immunosuppressive and immunostimulatory therapeutic strategies.

Other names

IL10RCD210Interleukin-10 receptor complexIL-10RA/IL-10RB heterodimerHIL-10R

Binding of IL-10 to the IL-10RA/IL-10RB heterodimer induces a conformational change that activates JAK1 and Tyk2. These kinases phosphorylate the cytoplasmic tail of IL-10RA, creating docking sites for STAT3, which is then phosphorylated, dimerizes, and translocates to the nucleus to regulate anti-inflammatory gene transcription (PubMed: 11121317).