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 cytokine-induced 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-γ and NK cell cytotoxicity. Thus, Srebp controls glucose metabolism in NK cells, and this Srebp-dependent regulation is critical for NK cell effector function.

中文翻译：

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Srebp控制的葡萄糖代谢对于NK细胞功能反应至关重要。

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，药理和代谢分析，我们证明了Srebp转录因子在细胞因子诱导的NK细胞代谢重编程中的重要作用，而与它们在脂质合成控制中的常规作用无关。Srebp是提高糖酵解和氧化磷酸化所必需的，并促进了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。防止Srebp的激活或直接抑制柠檬酸-苹果酸的穿梭抑制了干扰素-γ和NK细胞的细胞毒性的产生。因此，Srebp控制NK细胞中的葡萄糖代谢，