Details

Autor(en) / Beteiligte

• Fujiwara, Hideaki
• Seike, Keisuke
• Brooks, Michael D
• Mathew, Anna V
• Kovalenko, Ilya
• Pal, Anupama
• Lee, Ho-Joon
• Peltier, Daniel
• Kim, Stephanie
• Liu, Chen
• Oravecz-Wilson, Katherine
• Li, Lu
• Sun, Yaping
• Byun, Jaeman
• Maeda, Yoshinobu
• Wicha, Max S
• Saunders, Thomas L
• Rehemtulla, Alnawaz
• Lyssiotis, Costas A
• Pennathur, Subramaniam
• Reddy, Pavan

Titel

Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology

Ist Teil von

• Nature immunology, 2021-11, Vol.22 (11), p.1440-1451

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.