| First Author | Fujiwara H | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 11 | Pages | 1440-1451 |
| PubMed ID | 34686860 | Mgi Jnum | J:320341 |
| Mgi Id | MGI:6870550 | Doi | 10.1038/s41590-021-01048-3 |
| Citation | Fujiwara H, et al. (2021) Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology. Nat Immunol 22(11):1440-1451 |
| abstractText | 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. |
