The interleukin-23 receptor is a type I cytokine receptor. It is encoded in human by the IL23R gene.[5] In complex with the interleukin-12 receptor β1 subunit (IL-12Rβ1), it is activated by the cytokine interleukin 23 (IL-23).[6] The IL23R mRNA is 2.8 kilobases in length and includes 12 exons. The translated protein contains 629 amino acids; it is a type I penetrating protein and includes a signal peptide, an N-terminalfibronectin III-like domain and an intracellular part that contains three potential tyrosine phosphorylation domains.[6] There are 24 IL23R splice variants in mitogen-activated lymphocytes.[7]IL23R includes some single-nucleotide polymorphisms in the region encoding the domain that binds IL-23, which may lead to differences between people in Th17 activation.[8] There is also a variant of IL-23R that consists of just the extracellular part and is known as soluble IL-23R. This form can compete with the membrane-bound form to bind IL-23, modulating the Th17 immune response and regulation of inflammation and immune function.[9]
Function
The protein encoded by this gene is a subunit of the receptor for IL-23. This protein pairs with the receptor molecule IL-12Rβ1 (IL12RB1), together forming the IL-23 receptor complex, and both are required for IL-23 signaling. This protein associates constitutively with Janus kinase 2 (JAK2) and also binds to transcription activator STAT3 in a ligand-dependent manner.[5]
Clinical significance
Three variants in the IL23R gene have been shown to protect against Crohn's disease and ulcerative colitis.[10][11][12]
The effect of IL-23R variations present in the population have been studied with an in vitro expression model system.[13]
^de Paus RA, van de Wetering D, van Dissel JT, van de Vosse E (September 2008). "IL-23 and IL-12 responses in activated human T cells retrovirally transduced with IL-23 receptor variants". Molecular Immunology. 45 (15): 3889–95. doi:10.1016/j.molimm.2008.06.029. PMID18675459.
Zhang XY, Zhang HJ, Zhang Y, Fu YJ, He J, Zhu LP, Wang SH, Liu L (Jan 2006). "Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells". Immunogenetics. 57 (12): 934–43. doi:10.1007/s00251-005-0067-0. PMID16372191. S2CID35668044.
Orozco G, Rueda B, Robledo G, García A, Martín J (Aug 2007). "Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort". Human Immunology. 68 (8): 681–4. doi:10.1016/j.humimm.2007.05.008. PMID17678723.
Oliver J, Rueda B, López-Nevot MA, Gómez-García M, Martín J (Aug 2007). "Replication of an association between IL23R gene polymorphism with inflammatory bowel disease". Clinical Gastroenterology and Hepatology. 5 (8): 977–81, 981.e1–2. doi:10.1016/j.cgh.2007.05.002. hdl:10261/75893. PMID17678845.
