CRIF1 deficiency induces FOXP3^LOW inflammatory non-suppressive regulatory T cells, thereby promoting antitumor immunity.

ABSTRACT: Recently identified human FOXP3^lowCD45RA^- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (T_regs). In spite of their implication in tumors, the mechanism for generation of FOXP3^lowCD45RA^- INS cells in vivo is unclear. We showed that the FOXP3^lowCD45RA^- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in T_regs bore Foxp3^lowINS-T_regs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinfl

SUBMITTER: Lee S 

PROVIDER: S-EPMC10971410 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature