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- W4313430115 abstract "Abstract The intestinal microbiota is essential for instructing the host immune system, however, dysregulated immune responses to resident commensal microbes can promote pathologic inflammation. Despite this relationship, the mechanisms regulating tissue-intrinsic, microbiota-specific T cell responses remain poorly understood. Here, we find that non-hematopoietic intestinal epithelial cells (IECs) represent the dominant cells expressing major histocompatibility complex (MHC) II at the host-microbiota interface. Interestingly, epithelial MHCII and commensal-specific CD4+ T cells were simultaneously induced by post-natal microbiota colonization, prompting the hypothesis that epithelial MHCII regulates intestinal microbiota-specific CD4+ T cells. While classical MHCII-expressing antigen presenting cells promote antigen-specific T cell expansion, loss of IEC-intrinsic MHCII surprisingly resulted in elevated commensal-specific CD4+ T cells in the intestine. Further, epithelial MHCII actively limited accumulation of microbial-antigen specific CD4+ T cells in adult mice. Expansion of commensal-specific Th17 cells was restricted by epithelial MHCII, and remarkably mice lacking epithelial MHCII were highly susceptible to microbiota-triggered intestinal inflammation. Collectively, these data suggest that altered epithelial MHCII-T cell regulation in the intestine may impair tolerance to resident microbes and predispose to chronic inflammation. Future investigation into the relationship between the microbiota, IECs, and local immune cells could aid in the development of novel therapeutics to prevent or limit inflammatory conditions. This research is supported by the National Institutes of Health (DK114123, DK116868 and F32AI147591 to E.M.E.), Kenneth Rainin Foundation, and Burroughs Wellcome Fund. This project is supported in part by PHS grant P30 DK078392." @default.
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- W4313430115 date "2022-05-01" @default.
- W4313430115 modified "2023-10-16" @default.
- W4313430115 title "Epithelial MHC class II directs microbiota-specific intestinal immune homeostasis" @default.
- W4313430115 doi "https://doi.org/10.4049/jimmunol.208.supp.115.03" @default.
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