User:SimonsEM/Interleukin-10 receptor

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Interleukin-10 receptor (IL-10R) is a type II cytokine receptor. The receptor is tetrameric, composed of 2α and 2β subunits. The α subunit (encoded in the Il10ra gene) is expressed on haematopoietic cells (such as T, B, NK, mast, and dendritic cells) whilst the β subunit (encoded in the Il10rb gene) is expressed ubiquitously. The α subunit is exclusive to interleukin-10, however the β subunit is shared with other type-II cytokine receptors such as IL-22R, IL-26R and

INFλR [4].

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 [1]. There is evidence that upon ligand binding at the α subunit, a conformational change occurs in the β subunit that allows it to additionally connect to IL-10. This structure forms a heterotetramer that leads to the signaling complex activation of JAK1 and TYK2 kinases. JAK1 associates with the α subunit and TYK2 with the β subunit where they then phosphorylate portions of the α subunit. This recruits STAT3, which is also phosphorylated by JAK1 and TYK2. STAT3 homodimerizes, moves to the nucleus, and activates gene transcription [4].

The Interleukin-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 bowl 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 the α and β subunits were identified, some involving fully dysfunctional receptors, and some being incapable of accepting phosphorylation [4].


 * 1) Shouval, D.; Ouahed, J.; Biswas, A.; Goettel, J.; Horwitz, B.; Klein, C.; Muise, A.; Snapper, S. Chapter Five - Interleukin 10 Receptor Signaling: Master Regulator of Intestinal Mucosal Homeostasis in Mice and Humans, Advances in Immunology, 2014, 122, 177-210. https://doi.org/10.1016/B978-0-12-800267-4.00005-5.
 * 2) Reineke, U; Sabat, R; Volk, HD; Schneider-Mergener, J. Mapping of the interleukin-10/interleukin-10 receptor combining site. Protein Sci. 1998, 7(4), 951-960. doi:10.1002/pro.5560070412. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2143979/?tool=pmcentrez&report=abstract
 * 3) Kim, JH; Kang, TH; Noh, KH; et al. Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)-10 receptor enhances dendritic cell-based vaccine potency. Clin Exp Immunol. 2011,165(2),180-189. doi:10.1111/j.1365-2249.2011.04410.
 * 4) Spencer, S. D., Di Marco, F., Hooley, J., Pitts-Meek, S., Bauer, M., Ryan, A. M., Sordat, B., Gibbs, V. C., & Aguet, M. (1998). The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. The Journal of experimental medicine, 187(4), 571–578. https://doi.org/10.1084/jem.187.4.571
 * 5) Matsumoto, M. et al. (2014). Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity, 41. 1040-1051. http://dx.doi.org/10.1016/j.immuni.2014.10.016