Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells [ATAC-seq]

However, the role of the mitochondrial electron transport chain (ETC) in conventional DC subset function is poorly defined. Here, we revealed that immunogenic activation elevates late oxygen consumption in cDC1s, but not cDC2s.

To investigate the relevance of the ETC in DC immunogenicity, we generated mice with impaired ETC complex III function in DCs. ETC complex III impairment attenuated poised or adjuvant-triggered cDC1 activation, migration and capability to prime T cells for anti-cancer immunity, while it had a mild effect on cDC2s. Mechanistically, loss of complex III in cDC1s led to a deregulated redox and metabolite balance causing DNA hypermethylation of PU.1-binding regions.