IL10 RG gene

The IL10RB gene (IL10RB stands for Interleukin 10 Receptor Subunit Beta) is a protein coding gene located on chromosome 21q22.1. The protein encoded by this gene is a receptor unit (beta subunit of the IL10 receptor complex) for interleukin 10, and co-expression of this and the IL10RA protein has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. The receptor subunit IL10RA is located on chromosome 11q23.3.

The encoded receptor protein is structurally related to interferon receptors. It is part of the heterotetrameric assembly complex consisting of two subunits each of IL10RA and IL10RB and has been shown to mediate the immunosuppressive signal of interleukin 10 thereby inhibiting the synthesis of proinflammatory cytokines. Activation of this receptor leads to tyrosine phosphorylation of the kinases JAK1 and TYK2.

Diseases associated with mutaions in theIL10RB gene include.

• Inflammatory bowel disease 25, autosomal recessive (OMIM:612567); the deficiency is associated with a high percentage of skin diseases (Sharifinejad N et. al. 2022).

The encoded IL10RA protein forms a subunit of the IL10- cell surface receptor for the cytokine IL10. It is thus involved in all IL10-mediated anti-inflammatory functions limits excessive tissue destruction caused by inflammation. Upon binding to IL10, it triggers a conformational change in IL10RB that allows IL10RB to also bind IL10. The heterotetrameric assembly complex, which consists of two subunits of IL10RA and IL10RB, in turn activates the kinases JAK1 and TYK2, which are constitutively associated with IL10RA and IL10RB, respectively. These kinases then phosphorylate specific tyrosine residues in the intracellular domain of IL10RA, leading to recruitment and subsequent phosphorylation of STAT3. After phosphorylation, STAT3 forms a homodimer, migrates to the nucleus, and activates the expression of anti-inflammatory genes.

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2. Druszczyńska M et al (2022) Cytokine receptors-regulators of antimycobacterial immune response. Int J Mol Sci 23: 1112

3. Glocker EO et al (2009) Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. New Eng J Med 361: 2033-2045.
4. Mao H et al (2012) Exome sequencing identifies novel compound heterozygous mutations of IL-10 receptor 1 in neonatal-onset Crohn's disease. Genes Immun 13: 437-442.

5. Zheng C et al. (2019) Phenotypic Characterization of Very Early-Onset Inflammatory Bowel Disease with Interleukin 10 Signaling Deficiency: Based on a Large Cohort Study. Inflamm Bowel Dis 25:756-766.

6. Sharifinejad N et. al. (2022) The clinical, molecular, and therapeutic features of patients with IL10/IL10R deficiency: a systematic review. Clin Exp Immunol:uxac040.