Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments.
Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments.
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DOI：
10.1016/j.celrep.2018.03.084
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发表时间：
2018-04-17
期刊：
影响因子：
8.8
通讯作者：
Riley JL
中科院分区：
文献类型：
--
作者：
Ecker C;Guo L;Voicu S;Gil-de-Gómez L;Medvec A;Cortina L;Pajda J;Andolina M;Torres-Castillo M;Donato JL;Mansour S;Zynda ER;Lin PY;Varela-Rohena A;Blair IA;Riley JL
T细胞与恶性细胞竞争实体瘤微环境中有限的营养物质。我们发现效应记忆CD4 T细胞与其他T细胞亚群对限制葡萄糖的反应不同，并且可以在营养不良的环境中维持高水平的干扰素-γ（IFN-γ）产生。与幼稚（TN）或中枢记忆T（TCM）细胞不同，效应记忆T（TEM）细胞不能上调脂肪酸合成、氧化磷酸化和限制葡萄糖的还原性β-内酰胺酶解。初始T细胞中脂肪酸合成的干扰显著上调IFN-γ，而培养基中外源性脂质的增加抑制所有亚群的IFN-γ产生，表明脂肪酸代谢与糖酵解的相对比率是T细胞效应活性的直接预测因子。总之，这些数据表明，效应记忆T细胞被编程为具有有限的合成和代谢脂肪酸的能力，这使得它们能够在营养耗尽的微环境中维持T细胞功能。Ecker等人区分了葡萄糖限制期间初始和记忆T细胞亚群的独特代谢和功能特性。在葡萄糖饥饿期间，T细胞开始差异地依赖于脂肪酸合成和谷氨酰胺利用来存活。出乎意料的是，对脂肪酸合成的依赖改变了产生IFN-γ的能力。
T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ) production in a nutrient-poor environment. Unlike naive (TN) or central memory T (TCM) cells, effector memory T (TEM) cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments. Ecker et al. distinguish unique metabolic and functional properties of naive and memory T cell subsets during glucose limitation. During glucose starvation, T cells begin to differentially rely on fatty acid synthesis and glutamine utilization to survive. Unexpectedly, reliance on fatty acid synthesis alters the ability to produce IFN-γ.
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记忆CD8（+）T细胞使用细胞中性脂解来支持开发所需的代谢编程。
影响因子：
32.4
作者：
O'Sullivan, David;van der Windt, Gerritje J. W.;Huang, Stanley Ching-Cheng;Curtis, Jonathan D.;Chang, Chih-Hao;Buck, Michael D.;Qiu, Jing;Smith, Amber M.;Lam, Wing Y.;DiPlato, Lisa M.;Hsu, Fong-Fu;Birnbaum, Morris J.;Pearce, Edward J.;Pearce, Erika L.
通讯作者：
Pearce, Erika L.
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
64.5
作者：
Ho PC;Bihuniak JD;Macintyre AN;Staron M;Liu X;Amezquita R;Tsui YC;Cui G;Micevic G;Perales JC;Kleinstein SH;Abel ED;Insogna KL;Feske S;Locasale JW;Bosenberg MW;Rathmell JC;Kaech SM
通讯作者：
Kaech SM
影响因子：
29
作者：
Ma, Eric H.;Bantug, Glenn;Jones, Russell G.
通讯作者：
Jones, Russell G.