Mitochondrial C1qbp promotes differentiation of effector CD8⁺ T cells via metabolic-epigenetic reprogramming.

ABSTRACT: Early-activated CD8⁺ T cells increase both aerobic glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). However, whether and how the augmentation of OXPHOS regulates differentiation of effector CD8⁺ T cell remains unclear. Here, we found that C1qbp was intrinsically required for such differentiation in antiviral and antitumor immune responses. Activated C1qbp-deficient CD8⁺ T cells failed to increase mitochondrial respiratory capacities, resulting in diminished acetyl–coenzyme A as well as elevated fumarate and 2-hydroxyglutarate. Consequently, hypoacetylation of H3K27 and hypermethylation of H3K27 and CpG sites were associated with transcriptional down-regulation of effector signature genes. The effector differentiation of C1qbp-s

SUBMITTER: Zhai X 

PROVIDER: S-EPMC8641941 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature