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- W3205587507 abstract "Intestinal epithelial cell (IEC) damage by T cells contributes to graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis. But little is known about the target cell-intrinsic features that affect disease severity. Here we identified disruption of oxidative phosphorylation and an increase in succinate levels in the IECs from several distinct in vivo models of T cell-mediated colitis. Metabolic flux studies, complemented by imaging and protein analyses, identified disruption of IEC-intrinsic succinate dehydrogenase A (SDHA), a component of mitochondrial complex II, in causing these metabolic alterations. The relevance of IEC-intrinsic SDHA in mediating disease severity was confirmed by complementary chemical and genetic experimental approaches and validated in human clinical samples. These data identify a critical role for the alteration of the IEC-specific mitochondrial complex II component SDHA in the regulation of the severity of T cell-mediated intestinal diseases." @default.
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- W3205587507 date "2021-10-22" @default.
- W3205587507 modified "2023-10-16" @default.
- W3205587507 title "Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology" @default.
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- W3205587507 doi "https://doi.org/10.1038/s41590-021-01048-3" @default.
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