GOT1 regulates CD8+effector and memory T cell generation

被引：19

作者：

Xu, Wei ^{[1
,2
]}

Patel, Chirag H. ^{[1
,4
]}

Zhao, Liang ^{[1
]}

Sun, Im-Hong ^{[1
]}

Oh, Min-Hee ^{[3
]}

Sun, Im-Meng ^{[1
]}

Helms, Rachel S. ^{[1
]}

Wen, Jiayu ^{[1
]}

Powell, Jonathan D. ^{[1
,4
]}

机构：

[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Res Ctr, Bloomberg Kimmel Inst Canc Immunotherapy, Dept Oncol,Sch Med, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Sch Med, Baltimore, MD 21205 USA

[3] Yale Univ, Dept Immunobiol, New Haven, CT 06520 USA

[4] Calico LLC, San Francisco, CA 94080 USA

来源：

CELL REPORTS | 2023年 / 42卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ALPHA-KETOGLUTARATE; GLUTAMINE-METABOLISM; TRANSPORT;

D O I：

10.1016/j.celrep.2022.111987

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogram-ming 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 intra-cellular 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 a-ketoglutarate. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8+ T cells.

引用

页数：18

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