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• W2172119126 abstract "Abstract IL-10 contributes to the maintenance of intestinal homeostasis via the regulation of inflammatory responses to enteric bacteria. Loss of IL-10 signaling results in spontaneous colitis in mice and early onset enterocolitis in humans. Nucleotide-binding oligomerization domain (NOD) 2 is an intracellular receptor of bacterial peptidoglycan products, and, although NOD2 mutations are associated with Crohn’s disease, the precise role of NOD2 in the development of intestinal inflammation remains undefined. To determine the role of NOD2 in the development of colitis on the clinically relevant genetic background of IL-10–deficient signaling, we generated mice lacking IL-10 and NOD2 (IL-10−/−NOD2−/−). Loss of NOD2 in IL-10−/− mice resulted in significant amelioration of chronic colitis, indicating that NOD2 signaling promotes the development of intestinal inflammation in IL-10−/− mice. Contrary to previous reports investigating immune function in NOD2−/− mice, T cell proliferative capacity and IL-2 production were not impaired, and immune polarization toward type 1 immunity was not affected. However, loss of NOD2 in IL-10–deficient macrophages reduced IL-6, TNF-α, and IL-12p40 production in response to bacterial stimulation. Further analysis of the intrinsic macrophage response before the onset of inflammation revealed that, in the absence of IL-10, synergistic signaling between various TLRs and NOD2 resulted in hyperresponsive, proinflammatory macrophages, thus providing the appropriate immune environment for the development of colitis. Data presented in this study demonstrate that NOD2 signaling contributes to intestinal inflammation that arises through loss of IL-10 and provides mechanistic insight into the development of colitis in inflammatory bowel disease patients with impaired IL-10 signaling." @default.
• W2172119126 created "2016-06-24" @default.
• W2172119126 creator A5007033897 @default.
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• W2172119126 creator A5023286728 @default.
• W2172119126 creator A5043703885 @default.
• W2172119126 creator A5065341672 @default.
• W2172119126 date "2013-03-15" @default.
• W2172119126 modified "2023-10-16" @default.
• W2172119126 title "Nucleotide-Binding Oligomerization Domain 2 Signaling Promotes Hyperresponsive Macrophages and Colitis in IL-10–Deficient Mice" @default.
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• W2172119126 doi "https://doi.org/10.4049/jimmunol.1201332" @default.
• W2172119126 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3586975" @default.
• W2172119126 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23396949" @default.
• W2172119126 hasPublicationYear "2013" @default.
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