Refine
Has Fulltext
- yes (27)
Is part of the Bibliography
- yes (27)
Year of publication
Document Type
- Journal article (27)
Language
- English (27)
Keywords
- atherosclerosis (7)
- LASP1 (3)
- cytotoxic T cells (3)
- inflammation (3)
- 4D flow (2)
- AAA (2)
- CML (2)
- CXCR4 (2)
- WSS (2)
- aorta (2)
Institute
- Institut für Experimentelle Biomedizin (15)
- Institut für Klinische Biochemie und Pathobiochemie (7)
- Rudolf-Virchow-Zentrum (6)
- Medizinische Klinik und Poliklinik I (5)
- Physikalisches Institut (4)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (3)
- Institut für Anatomie und Zellbiologie (2)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (2)
- Theodor-Boveri-Institut für Biowissenschaften (2)
- Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde (1)
T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells. At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. Our findings also bear clinical significance, as metabolic engineering of chimeric antigen receptor (CAR) T cells is a promising strategy to enhance the stemness and functionality of Tpex cells for cancer immunotherapy.