Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells

Zhilin Hu, Guojun Qu, Xiaoyan Yu, Haojie Jiang, Xiao Lu Teng, Lei Ding, Qianwen Hu, Xinwei Guo, Yan Zhou, Feng Wang, Hua Bing Li, Lei Chen, Jin Jiang, Bing Su, Junling Liu, Q. Zou

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

CD8+ T cell expansions and functions rely on glycolysis, but the mechanisms underlying CD8+ T cell glycolytic metabolism remain elusive. Here, we show that acylglycerol kinase (AGK) is required for the establishment and maintenance of CD8+ T cell metabolic and functional fitness. AGK deficiency dampens CD8+ T cell antitumor functions in vivo and perturbs CD8+ T cell proliferation in vitro. Activation of phosphatidylinositol-3-OH kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, which mediates elevated CD8+ T cell glycolysis, is tightly dependent on AGK kinase activity. Mechanistically, T cell antigen receptor (TCR)- and CD28-stimulated recruitment of PTEN to the plasma membrane facilitates AGK-PTEN interaction and AGK-triggered PTEN phosphorylation, thereby restricting PTEN phosphatase activity in CD8+ T cells. Collectively, these results demonstrate that AGK maintains CD8+ T cell metabolic and functional state by restraining PTEN activity and highlight a critical role for AGK in CD8+ T cell metabolic programming and effector function. Hu et al. show a critical role of acylglycerol kinase (AGK) in the establishment and maintenance of CD8+ T cell metabolic and functional fitness. AGK promotes the activation of PI3K-mTOR signaling to mediate CD8+ T cell glycolysis and antitumor functions by restricting PTEN phosphatase activity.

Original languageEnglish (US)
Pages (from-to)290-302.e5
JournalCell Metabolism
Volume30
Issue number2
DOIs
Publication statusPublished - Aug 6 2019

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Keywords

  • AGK
  • CD8+ T cells
  • glycolysis
  • PI3K-mTOR
  • PTEN

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Hu, Z., Qu, G., Yu, X., Jiang, H., Teng, X. L., Ding, L., ... Zou, Q. (2019). Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells. Cell Metabolism, 30(2), 290-302.e5. https://doi.org/10.1016/j.cmet.2019.05.016