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• W1625376987 endingPage "5582" @default.
• W1625376987 startingPage "5578" @default.
• W1625376987 abstract "IL-10-deficient mice exhibit spontaneous enterocolitis and other symptoms akin to Crohn's disease, indicating that IL-10 might regulate normal physiology in the gut. However, clinical trials with IL-10 in Crohn's disease were disappointing, although some patients showed healing of intestinal mucosa. This study searched for genetic polymorphisms within the IL-10 pathway. We decided to screen for mutations of the IL-10R1 cDNA in healthy volunteers and Crohn's disease patients and identified two novel variants: a serine 138-to-glycine (S138G) and a glycine 330-to-arginine (G330R) substitution. The allelic frequency in a European cohort was relatively high (16% for the S138G and 33% for the G330R), and S138G was in strong linkage disequilibrium with G330R. A similar allele frequency was found in a group of Crohn's patients. In IL-10R1 G330R-expressing monocytes, the inhibitory effect of IL-10 on TNF-alpha production was diminished, indicating that this variant may be a loss-of-function allele. No such difference was observed between haplotypes 4 (G330R only) and 7 (S138G and G330R). In addition, these IL-10R1 variants had no influence on the IL-10R1 expression density. Structural analysis of the S138G variant revealed that the substitution of S138G may interfere with binding of IL-10 to IL-10R1." @default.
• W1625376987 created "2016-06-24" @default.
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• W1625376987 date "2003-06-01" @default.
• W1625376987 modified "2023-10-09" @default.
• W1625376987 title "Novel Variants of the IL-10 Receptor 1 Affect Inhibition of Monocyte TNF-α Production" @default.
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• W1625376987 doi "https://doi.org/10.4049/jimmunol.170.11.5578" @default.
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