Interleukin-10 receptor (IL-10R) is a type II cytokine receptor. The receptor is tetrameric, composed of 2α[1] and 2β[2] 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.[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 the α subunit, a conformational change occurs in the β subunit that allows it to additionally bind 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 additionally phosphorylated by JAK1 and TYK2. STAT3 homodimerizes, moves to the cellular nucleus, and activates gene transcription.[3]
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 possessing fully dysfunctional receptors, and others being incapable of accepting phosphorylation.[3]
References
- ^ Liu Y, Wei SH, Ho AS, de Waal Malefyt R, Moore KW (February 1994). "Expression cloning and characterization of a human IL-10 receptor". Journal of Immunology. 152 (4): 1821–1829. doi:10.4049/jimmunol.152.4.1821. PMID 8120391. S2CID 21873341.
- ^ Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S (October 1997). "Identification and functional characterization of a second chain of the interleukin-10 receptor complex". The EMBO Journal. 16 (19): 5894–5903. doi:10.1093/emboj/16.19.5894. PMC 1170220. PMID 9312047.
- ^ a b c Spencer SD, Di Marco F, Hooley J, Pitts-Meek S, Bauer M, Ryan AM, et al. (February 1998). "The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor". The Journal of Experimental Medicine. 187 (4): 571–578. doi:10.1084/jem.187.4.571. PMC 2212143. PMID 9463407.
- ^ 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. ISBN 9780128002674. PMC 4741283. PMID 24507158.
External links
- Receptors,+Interleukin-10 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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This page was last edited on 13 January 2024, at 11:54