Srebp-controlled glucose metabolism is essential for NK cell functional responses
Srebp-controlled glucose metabolism is essential for NK cell functional responses
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DOI：
10.1038/ni.3838
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发表时间：
2017-11-01
影响因子：
30.5
通讯作者：
Finlay, David K.
中科院分区：
文献类型：
--
作者：
Assmann, Nadine;O'Brien, Katie L.;Finlay, David K.
活化的自然杀伤（NK）细胞参与正常效应子功能所需的强大代谢反应。使用遗传，药理学和代谢分析，我们证明了Srebp转录因子在尼古丁诱导的NK细胞代谢重编程中的重要作用，这与它们在脂质合成控制中的常规作用无关。Srebp是糖酵解和氧化磷酸化升高所必需的，并促进了一种独特的代谢途径构型，其中葡萄糖通过柠檬酸-苹果酸穿梭代谢为胞质柠檬酸。阻止Srebp的激活或直接抑制柠檬酸-苹果酸穿梭抑制了干扰素-γ的产生和NK细胞的细胞毒性。因此，Srebp控制NK细胞中的葡萄糖代谢，并且这种Srebp依赖性调节对于NK细胞效应子功能至关重要。
Activated natural killer (NK) cells engage in a robust metabolic response that is required for normal effector function. Using genetic, pharmacological and metabolic analyses, we demonstrated an essential role for Srebp transcription factors in cytokineinduced metabolic reprogramming of NK cells that was independent of their conventional role in the control of lipid synthesis. Srebp was required for elevated glycolysis and oxidative phosphorylation and promoted a distinct metabolic pathway configuration in which glucose was metabolized to cytosolic citrate via the citrate-malate shuttle. Preventing the activation of Srebp or direct inhibition of the citrate-malate shuttle inhibited production of interferon-gamma and NK cell cytotoxicity. Thus, Srebp controls glucose metabolism in NK cells, and this Srebp-dependent regulation is critical for NK cell effector function.