2026-09-14T22:39:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/277052026-09-12T00:17:12Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Heras-Murillo, Ignacio author Mañanes, Diego author Calafell-Segura, Josep author Belinchón García, Adrián author Borràs-Eroles, Clara author Munné, Pablo author Mastrangelo, Annalaura author Martínez-Cano, Sarai author Hernansanz-Agustín, Pablo author Zuriaga, María A author Fuster, José J author Szibor, Marten author Melero, Ignacio author Enríquez, José Antonio author Chandel, Navdeep S author Ballestar, Esteban author Wculek, Stefanie K author Sancho, David author 2026-06-02 Activation of conventional dendritic cells (cDCs) favors increased glycolysis-driven lactic fermentation, while oxidative phosphorylation (OXPHOS) links to tolerance. Here, selective targeting of the mitochondrial electron transport chain (ETC) in cDCs uncovers a critical role for OXPHOS in regulating their immunogenicity. Disruption of ETC complex III dampens adjuvant-triggered primary human and mouse cDC1 activation and their capability to prime T cells for anti-cancer immunity, while it has a milder effect on cDC2s. Mechanistically, complex III impairment in cDC1s leads to a dysregulated redox and metabolite balance, altering DNA methylation of PU.1 and activator-protein-1 (AP-1) binding regions. These epigenetic changes hinder the rapid induction of immediate-early stimulus-induced genes in cDC1s upon stimulation. The reduced immunogenic responsiveness of ETC-impaired cDC1s can be rescued by ectopic expression of alternative oxidase and phenocopied by Tet2 deficiency. Our findings reveal that electron flow through the ETC maintains a poised activation state in cDC1s, essential for effective anti-tumor immunity. Cell Metab. 2026 Jun 2;38(6):1097-1112.e8. CELL METABOLISM 41990746 https://hdl.handle.net/20.500.12105/27705 DNA methylation dendritic cells electron transport chain immunity metabolites mitochondria redox balance Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells.