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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 | Qiang Zou
Cell metabolism | 2019

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.

Pubmed ID: 31204281

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