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Srebp-controlled glucose metabolism is essential for NK cell functional responses

机译:Srebp控制的葡萄糖代谢对于NK细胞功能反应至关重要

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摘要

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.
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  • 来源
    《Nature immunology》 |2017年第11期|共10页
  • 作者单位

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Univ Regensburg Inst Funct Genom Regensburg Germany;

    Univ Regensburg Inst Funct Genom Regensburg Germany;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

    Univ Regensburg Inst Funct Genom Regensburg Germany;

    Trinity Coll Dublin Trinity Biomed Sci Inst Sch Biochem &

    Immunol Dublin Ireland;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

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