GOT1 regulates CD8⁺ effector and memory T cell generation.

ABSTRACT: T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-¹³C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8⁺ T cell effector differentiation and function. Mechanistically, GOT1 enhances proliferation by maintaining intracellular redox balance and serine-mediated purine nucleotide biosynthesis. Further, GOT1 promotes the glycolytic programming and cytotoxic function of cytotoxic T lymphocytes via posttranslational regulation of HIF protein, potentially by regulating the levels of α-ketoglutarate. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8⁺ T cells.

SUBMITTER: Xu W 

PROVIDER: S-EPMC9943022 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature