Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells - PubMed
3 hours ago
- #dendritic cells
- #immunogenicity
- #mitochondrial metabolism
- Mitochondrial metabolism regulates dendritic cell (cDC) immunogenicity, with oxidative phosphorylation (OXPHOS) linked to tolerance and glycolysis to activation.
- Disruption of electron transport chain (ETC) complex III in cDC1s dampens activation and T cell priming for anti-cancer immunity, with milder effects on cDC2s.
- Complex III impairment causes redox and metabolite imbalances, altering DNA methylation at PU.1 and AP-1 regions, hindering rapid gene induction upon stimulation.
- The reduced immunogenicity in ETC-impaired cDC1s can be rescued by alternative oxidase expression or phenocopied by Tet2 deficiency.
- Electron flow through the ETC maintains a poised activation state in cDC1s, crucial for effective anti-tumor immunity.