IL10, also known as CSIF, was first reported in relation to autosomal recessive early-onset inflammatory bowel disease (IBD) in 2010 (Glocker EO, et al., PMID: 20934598). Individuals reported to date with IL10-associated early-onset IBD have presented with IBD with an onset between 1 month and 5 years of age without additional characteristic features.
Three variants (missense) that have been reported in four unrelated probands in three publications (PMIDs: 20934598, 22549091, 29248579) are included in this curation. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by animal models, expression studies, and in vitro functional assays (PMIDs: 8770874, 9312047, 15534372, 1578140, 17137799, 1827484, 22549091, 23158016). IL10 is a well-established anti-inflammatory cytokine (PMID: 1827484, 1578140, 33691712). In vitro experiments have demonstrated that mutant IL10 carrying patient-associated variants displayed impaired suppression of TNFa production by stimulated PBMCs (PMID: 22549091, 23158016). Multiple mouse models of IL10 deficiency, including IL10-knockout and CD4-specific IL10 knockout mice, recapitulate the spontaneous intestinal inflammation in human disease (PMID: 8770874, 15534372). Notably, both IL10Ra and IL10RB, the subunits of the receptor with which IL10 directly interacts (PMID: 9312047), are also associated with early-onset IBD (PMID: 39795980).
In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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