Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells
Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells
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酰基甘油激酶维持 CD8( ) T 细胞的代谢状态和免疫反应
DOI：
10.1016/j.cmet.2019.05.016
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发表时间：
2019-08-06
期刊：
影响因子：
29
通讯作者：
Zou, Qiang
中科院分区：
文献类型：
--
作者：
Hu, Zhilin;Qu, Guojun;Zou, Qiang
CD8(+) T细胞的扩增和功能依赖于糖酵解，但CD8(+) T细胞糖酵解代谢的机制尚不清楚。在这里，我们发现酰基甘油激酶（AGK）是建立和维持CD8(+) T细胞代谢和功能适应度所必需的。AGK缺乏在体内抑制CD8(+) T细胞抗肿瘤功能，并在体外干扰CD8(+) T细胞的增殖。磷脂酰肌醇-3- oh激酶(PI3K)-哺乳动物雷帕霉素（mTOR）信号传导靶点，介导CD8(+) T细胞糖酵解升高，其激活紧密依赖于AGK激酶活性。从机制上讲，T细胞抗原受体(TCR)-和cd28刺激PTEN向质膜募集，促进AGK-PTEN相互作用和agk触发的PTEN磷酸化，从而限制CD8(+) T细胞中PTEN磷酸酶的活性。综上所述，这些结果表明AGK通过抑制PTEN活性来维持CD8(+) T细胞的代谢和功能状态，并突出了AGK在CD8(+) T细胞代谢编程和效应功能中的关键作用。
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.