GOT1 regulates CD8+ effector and memory T cell generation

Wei Xu; Chirag H. Patel; Liang Zhao; Im-Hong Sun; Min-Hee Oh; Im-Meng Sun; Rachel S. Helms; Jiayu Wen; Jonathan D. Powell

Cell Reports (Jan 2023)

GOT1 regulates CD8+ effector and memory T cell generation

Wei Xu,
Chirag H. Patel,
Liang Zhao,
Im-Hong Sun,
Min-Hee Oh,
Im-Meng Sun,
Rachel S. Helms,
Jiayu Wen,
Jonathan D. Powell

Affiliations

Wei Xu: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Chirag H. Patel: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Calico LLC, South San Francisco, CA 94080, USA
Liang Zhao: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Im-Hong Sun: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Min-Hee Oh: Department of Immunobiology, Yale University, New Haven, CT 06520, USA
Im-Meng Sun: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Rachel S. Helms: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Jiayu Wen: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Jonathan D. Powell: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Calico LLC, South San Francisco, CA 94080, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 1
p. 111987

Abstract

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Summary: 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.

CP: Metabolism

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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