T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses

Koji Toriyama, Makoto Kuwahara, Hiroshi Kondoh, Takumi Mikawa, Nobuaki Takemori, Amane Konishi, Toshihiro Yorozuya, Takeshi Yamada, Tomoyoshi Soga, Atsushi Shiraishi, Masakatsu Yamashita

Research output: Contribution to journalArticle

Abstract

Although the important roles of glycolysis in T cells have been demonstrated, the regulatory mechanism of glycolysis in activated T cells has not been fully elucidated. Furthermore, the influences of glycolytic failure on the T cell-dependent immune response in vivo remain unclear. We therefore assessed the role of glycolysis in the T cell-dependent immune response using T cell-specific Pgam1-deficient mice. Both CD8 and CD4 T cell-dependent immune responses were attenuated by Pgam1 deficiency. The helper T cell-dependent inflammation was ameliorated in Pgam1-deficient mice. Glycolysis augments the activation of mTOR complex 1 (mTORC1) and the T-cell receptor (TCR) signals. Glutamine acts as a metabolic hub in activated T cells, since the TCR-dependent increase in intracellular glutamine is required to augment glycolysis, increase mTORC1 activity and augment TCR signals. These findings suggest that mTORC1, glycolysis and glutamine affect each other and cooperate to induce T cell proliferation and differentiation.

Original languageEnglish
Article number394
JournalCommunications biology
Volume3
Issue number1
DOIs
Publication statusPublished - 2020 Dec 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

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    Toriyama, K., Kuwahara, M., Kondoh, H., Mikawa, T., Takemori, N., Konishi, A., Yorozuya, T., Yamada, T., Soga, T., Shiraishi, A., & Yamashita, M. (2020). T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses. Communications biology, 3(1), [394]. https://doi.org/10.1038/s42003-020-01122-w