GOT1 regulates CD8(+) effector and memory T cell generation

T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-(13)C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8(+) T cell effector differentiation and function. Mechanistically, GOT1 enhances...

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Detalles Bibliográficos
Autores principales: Xu, Wei, Patel, Chirag H., Zhao, Liang, Sun, Im-Hong, Oh, Min-Hee, Sun, Im-Meng, Helms, Rachel S., Wen, Jiayu, Powell, Jonathan D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9943022/
https://www.ncbi.nlm.nih.gov/pubmed/36640309
http://dx.doi.org/10.1016/j.celrep.2022.111987
Descripción
Sumario:T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-(13)C]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.

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