Interleukin-10 receptor (IL-10R) is atype II cytokine receptor. The receptor istetrameric, composed of 2α[1] and 2β[2] subunits. Theα subunit (encoded in theIl10ra gene) is expressed on haematopoietic cells (such as T, B, NK, mast, anddendritic cells) whilst theβ subunit (encoded in theIl10rb gene) is expressed ubiquitously. Theα subunit is exclusive tointerleukin-10, however theβ subunit is shared with othertype II cytokine receptors such asIL-22R,IL-26R and INFλR.[3]
The IL-10Rα subunit acts as the ligand binding site and may be upregulated in various cell types as necessary. The IL-10Rβ functions as the signaling subunit and is constitutively expressed in a majority of cell types.[4] There is evidence that upon ligand binding at theα subunit, a conformational change occurs in theβ subunit that allows it to additionally bind toIL-10. This structure forms aheterotetramer that leads to the signaling complex activation ofJAK1 andTYK2 kinases.JAK1 associates with theα subunit, andTYK2 with theβ subunit where they then phosphorylate portions of theα subunit. This recruitsSTAT3, which is additionally phosphorylated byJAK1 andTYK2.STAT3 homodimerizes, moves to the cellular nucleus, and activates gene transcription.[3]
TheInterleukin-10 receptor is implicated in regulation of gastro-intestinal immune response, primarily in the mucosal layer. Murine studies of test subjects lacking functional receptors showed rapid onset of bowel inflammatory disorders. In human studies, the early onset of irritable bowel disease has been correlated with defects in the IL-10R subunits. Cases involving both theα andβ subunits were identified, some possessing fully dysfunctional receptors, and others being incapable of accepting phosphorylation.[3]
^Shouval DS, Ouahed J, Biswas A, Goettel JA, Horwitz BH, Klein C, et al. (2014-01-01). Alt FW (ed.).Interleukin 10 receptor signaling: master regulator of intestinal mucosal homeostasis in mice and humans. Advances in Immunology. Vol. 122. Academic Press. pp. 177–210.doi:10.1016/b978-0-12-800267-4.00005-5.ISBN9780128002674.PMC4741283.PMID24507158.
