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- W2783156919 abstract "IBD is driven by excessive inflammation involving reciprocal interactions between innate and adaptive immune cells. To better understand how innate immunity contributes to IBD, colitis models that occur in the absence of adaptive immunity are needed. TNFAIP3 is a cytosolic protein that blocks innate immune receptor activation of NF-kappaB and MAPK pathways. We generated villin-TNFAIP3 mice to investigate its role in intestinal epithelial cells. We crossed these mice to mice lacking adaptive immune cells (RAG1-/-) and discovered that these mice develop colitis. All mice are C57Bl/6. v-TNFAIP3 mice and RAG1-/- mice were interbred (TRAG mice) and colitis was assessed. Antibiotics were given to investigate the role of microbes. Anti-TNF and anti-Thy1 treatments were used to test the role of TNF and innate lymphoid cell (ILCs). Rorc-/- mice were used to test the role of ILC3s. LPLs and cytokines were measured in mucosal tissues. villin-TNFAIP3 x RAG1-/- mice (TRAG mice) developed 100% penetrant early onset colitis which was prevented by antibiotics but not by anti-TNF treatment. Inflammation was restricted to the colon and not transmissible to RAG1-/- or TNFAIP3 littermates. TRAG colitis involved increased mucosal infiltration of ILCs and was prevented by anti-Thy1 antibody treatment. TRAG colitis was not prevented on a ILC3-deficient (Rorc-/-) background. The colitis in TRAG mice was characterized by increased expression of IFNg and IFNg-target genes. We are therefore investigating whether innate immune colitis in TRAG mice is driven by IFNg and potentially ILC1 cells. This is a new robust model of colitis that occurs spontaneously in the absence of adaptive immune cells, is driven by microbes but is not transmissible, and is also driven by ILC but occurs in the absence of ILC3s. Further investigation of this model will provide new insight into innate immune mechanisms that drive colitis." @default.
- W2783156919 created "2018-01-26" @default.
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- W2783156919 date "2018-01-01" @default.
- W2783156919 modified "2023-09-25" @default.
- W2783156919 title "P006 A NEW MODEL OF SPONTANEOUS INNATE IMMUNE MEDIATED COLITIS" @default.
- W2783156919 doi "https://doi.org/10.1053/j.gastro.2017.11.038" @default.
- W2783156919 hasPublicationYear "2018" @default.
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