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GOT1 regulates CD8+ effector and memory T cell generation.

Wei Xu1, Chirag H Patel2, Liang Zhao3

  • 1Bloomberg∼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.

Cell Reports
|January 14, 2023
PubMed
Summary
This summary is machine-generated.

Glutamine oxaloacetate transaminase 1 (GOT1) is crucial for CD8+ T cell effector functions, enhancing proliferation and cytotoxicity. Its absence promotes memory CD8+ T cell generation.

Keywords:
CP: MetabolismGOT1HIFNADH/NADeffector and memory CD8(+) T cellglucoseglutamateserine

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Area of Science:

  • Immunology
  • Cellular Metabolism
  • T cell biology

Background:

  • T cell activation, proliferation, function, and differentiation depend on metabolic regulation.
  • The role of specific metabolic enzymes in T cell fate remains an active area of research.

Purpose of the Study:

  • To investigate the role of Glutamine oxaloacetate transaminase 1 (GOT1) in CD8+ T cell metabolism and function.
  • To elucidate the mechanisms by which GOT1 influences T cell differentiation and effector functions.

Main Methods:

  • Utilized [U-13C]glucose tracing to track metabolic pathways in T cells.
  • Employed genetic deletion of GOT1 to assess its impact on T cell populations.
  • Analyzed T cell proliferation, effector function, and memory cell generation.

Main Results:

  • GOT1 is critical for CD8+ T cell effector differentiation and function.
  • GOT1 enhances T cell proliferation by maintaining redox balance and serine-mediated purine biosynthesis.
  • GOT1 promotes glycolytic programming and cytotoxic activity via posttranslational regulation of HIF protein.
  • Genetic deletion of GOT1 leads to increased generation of memory CD8+ T cells.

Conclusions:

  • GOT1 plays a dual role in CD8+ T cell biology, promoting effector functions while its absence favors memory cell development.
  • Targeting GOT1 could be a strategy to modulate T cell responses for therapeutic applications.