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- W4313382698 abstract "Abstract AIRE-dependent expression of tissue-specific antigens by medullary thymic epithelial cells allows for the selection of non-autoreactive T cells, supporting self-tolerance. Although gut microbiota is known to educate the immune system, balancing effector and regulatory T cells responses, it remains unknown how bacteria-specific T cells are selected. Here we studied how thymic T cell development is altered after colonization with model intestinal microbes. Colonization of mice at weaning induced thymic expansion of bacteria-specific naive T cells. Remarkably, bacterial DNA was found in the thymus of colonized mice and 16s rDNA sequencing identified bacterial DNA from a broad range of intestinal microbes in the thymus of steady-state mice. We identified enrichment of CX3CR1+ dendritic cells (CX3+ DCs) after microbial colonization and depleting these cells or inhibiting their antigen-presentation suppressed induction of bacteria-specific T cells. Further, depletion of the gut microbiota with antibiotics reduced positive selection, bacterial 16s, and CX3+ DCs in the thymus. In older mice, we did not observe microbial DNA in the thymus, altered CX3+ DCs, or expansion of microbiota specific T cells, indicating a developmental window where intestinal microbes can regulate thymic output. Using models of microbiota-specific T cell immunity or pathogen infection, we demonstrate thymic microbiota-specific T cells can differentiate into intestinal effector T cells, offering protection or mediating pathology. Together, our data suggests trafficking of bacteria to the thymus by intestinal DCs drives T cell selection of microbiota-specific T cells to shape peripheral immunity against pathogens and the microbiota itself." @default.
- W4313382698 created "2023-01-06" @default.
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- W4313382698 date "2020-05-01" @default.
- W4313382698 modified "2023-09-23" @default.
- W4313382698 title "Early life selection of gut microbiota specific T cells" @default.
- W4313382698 doi "https://doi.org/10.4049/jimmunol.204.supp.84.1" @default.
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