Filtern
Volltext vorhanden
- ja (8)
Gehört zur Bibliographie
- ja (8)
Dokumenttyp
Sprache
- Englisch (8)
Schlagworte
- cytotoxic T cells (2)
- ADP-ribosylation toxins (1)
- Activation induced cell death/AICD (1)
- Alpha therapy (1)
- Anergy (1)
- Apoptosis (1)
- Autoimmune diseases (1)
- Bone marrow transplantantation (1)
- C3 (1)
- CRAC (1)
- Ca2+ (1)
- Calcineurin (1)
- Expression (1)
- Factor receptor (1)
- Graft-versus-leukemia (1)
- Medizin (1)
- NF-κB (1)
- NFATc (1)
- NFATc1 (1)
- NFATc1/αA (1)
- Notch1 (1)
- OBF-1 OCA-B (1)
- OCT-1-deficient mice (1)
- Proliferation (1)
- Regulatory-cells (1)
- Rheumatoid arthritis (1)
- STIM1 (1)
- STIM2 (1)
- Suppression (1)
- T cell acute lymphoblastic leukemia (1)
- T-ALL (1)
- Tumor-necrosis-factor (1)
- actin filaments (1)
- anemia (1)
- bacterial toxins (1)
- botulinum C2 toxin (1)
- calcium (1)
- cellular uptake (1)
- channel (1)
- clostridium botulinum (1)
- coactivator OBF-1 (1)
- embryonic lethality (1)
- endothelial cells (1)
- functional characterization (1)
- gene expression (1)
- gene regulation (1)
- germinal center formation (1)
- immune cells (1)
- immunoglobulin promoters (1)
- infection (1)
- inflammation (1)
- interferon (1)
- lymphocyte activation (1)
- lymphocyte differentiation (1)
- macrophages (1)
- mammalian cells (1)
- membrane translocation (1)
- mitochondrial calcium uniporter (1)
- murine homolog (1)
- regulatory T cells (1)
- ribosyltransferase (1)
- signal transduction (1)
- suppressive capacity (1)
- translational research (1)
Institut
- Pathologisches Institut (5)
- Institut für Virologie und Immunbiologie (3)
- Institut für Systemimmunologie (2)
- Medizinische Klinik und Poliklinik II (2)
- Theodor-Boveri-Institut für Biowissenschaften (2)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (1)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (1)
- Institut für Experimentelle Biomedizin (1)
- Julius-von-Sachs-Institut für Biowissenschaften (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.