Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology.
Nat Immunol
; 22(11): 1440-1451, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34686860
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Colite
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Colo
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Citotoxicidade Imunológica
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Complexo II de Transporte de Elétrons
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Células Epiteliais
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Doença Enxerto-Hospedeiro
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Mucosa Intestinal
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Mitocôndrias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos