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Srebp-controlled glucose metabolism is essential for NK cell functional responses.
Nature Immunology ( IF 27.7 ) Pub Date : 2017-Nov-01 , DOI: 10.1038/ni.3838
Nadine Assmann , Katie L O'Brien , Raymond P Donnelly , Lydia Dyck , Vanessa Zaiatz-Bittencourt , Róisín M Loftus , Paul Heinrich , Peter J Oefner , Lydia Lynch , Clair M Gardiner , Katja Dettmer , David K Finlay

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:

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,
更新日期:2017-09-18
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