Cytoplasmic DNA sensing boosts CD4⁺ T cell metabolism for inflammatory induction.

ABSTRACT: DNA accumulation is associated with the development of autoimmune inflammatory diseases. However, the pathological role and underlying mechanism of cytoplasmic DNA accumulation in CD4⁺ T cells have not been well established. Here, we show that Trex1 deficiency-induced endogenous DNA accumulation in CD4⁺ T cells greatly promoted their induction of autoimmune inflammation in a lupus-like mouse model. Mechanistically, the accumulated DNA in CD4⁺ T cells was sensed by the KU complex, then triggered the activation of DNA-PKcs and ZAK and further facilitated the activation of AKT, which exacerbated glycolysis, thereby promoting the inflammatory responses. Accordingly, blocking the DNA sensing pathway in CD4⁺ T cells by genetic knockout of Zak

SUBMITTER: Ye J 

PROVIDER: S-EPMC11749111 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature