Alt. symbols: CRFB4 | D21S58 | D21S66 | CRF2-4 | CDW210B | IL-10R2

Approved name: interleukin 10 receptor subunit beta
Alt. names: interleukin 10 receptor, beta

Location: 21q22.11: 33266367 - 33311420 (+)
Gene type: protein_coding, 9 transcripts.

Scores: LoFtool: 0.558000 | pLI: 0.00033479 | LOEUF: 1.115

HGNC: 5965

NCBI: 3588, RefSeq: NG_012089.1

Ensembl: ENSG00000243646.11

LRG_152 | Status: public

OMIM: 123889

Expression | ProteinAtlas

IL10RB encodes a receptor subunit shared by and required for the activation of five class 2 cytokines: IL-10, IL-22, IL-26, IL-28, and IFN-L1. This receptor, which is structurally related to the interferon receptors and thus plays a role in regulating anti-viral immunity, has been shown to mediate the immunosuppressive signaling of IL-10, as well as to promote myeloid progenitor cell survival through the insulin receptor substrate-2/PI 3-kinase/AKT pathway (PMID: 11591769). Upon alpha subunit engagement by IL-10, a conformational change occurs in the beta subunit of the receptor to allowing the latter to bind IL-10 as well (PMID: 16982608). Then, this heterotetrameric complex, composed of two alpha and two beta subunits, activates the constitutively associated kinases JAK1 and TYK2 (PMID: 12133952), which then phosphorylate specific tyrosine residues in the intracellular domain of the alpha subunit, leading to STAT3 recruitment and phosphorylation. Phosphorylated STAT3 then homodimerizes, translocates to the nucleus, and activates the expression of anti-inflammatory genes. This pathway may also prevent starvation-induced autophagy in fibroblasts via crosstalk with mTOR-AKT signaling (PMID: 26962683). Most recently, elevated IL10RB expression in the blood has been associated with unfavorable host outcomes in COVID-19 infection (PMID: 34100031).

Biallelic LOF mutations in genes encoding either IL-10 (IL10) or its receptors (IL10RA for IL-10R1 and IL10RB for IL-10R2) have been associated with autosomal recessive forms of early or very early onset inflammatory bowel disease (V/EO-IBD) [OMIM: 612567, 613148]. In addition to severe and progressive colitis presenting as bloody diarrhea often within the first 3 months of life, patients also have failure to thrive, recurrent fevers and infections, abscesses and perianal fistula formation, oral aphthous lesions, folliculitis, and arthritis (PMID: 20934598, 22549091). Immunophenotyping shows grossly normal lymphocyte numbers and T cell proliferative responses, along with normal specific antibody responses to vaccinations but elevated IgG, IgA, and IgM levels in some patients. In patients with IL10 deficiency, circulating IL-10 levels are expectedly low to absent, but in patients with deficiencies in the receptor subunits, serum IL-10 levels may be normal or elevated (PMID: 19890111, 21519361, 22476154). Because patients with these conditions often have severe, treatment-refractory IBD, early consideration should be given to HSCT (PMID: 23158016). Moreover, patients appear to also have predisposition towards the development of B-cell lymphomas (PMID: 24089328). Unlike IL10RA mutations, which are predominantly missense, IL10RB mutations are often recurrent nonsense mutations (S230X, W204X, W159X, E141X), though some splice site and frameshift mutations as well as one recent missense mutation have also been reported (PMID: 19890111, 21519361, 22549091, 25373860, 31096038). Interestingly, no response to IL-10 was observed for 2 patients with mutations in the alpha (R262C) or beta (E141X) chain of IL10R, respectively, although a fully functional Jak-STAT3 pathway was present (PMID: 21519361). The patient with absent IL10RB was unable to upregulate protective transcripts in response to IL-22, whereas all other EO-IBD patients, including the patient with an abnormal alpha chain, responded normally. [Load More]