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标题：Conditional Deletion of PGC-1α Results in Energetic and Functional Defects in NK Cells
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作者：Zachary J. Gerbec ; Elaheh Hashemi ; Arash Nanbakhsh 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：9
页码：1-44
DOI：10.1016/j.isci.2020.101454
语种：English
出版社：Elsevier
摘要：SummaryDuring an immune response, natural killer (NK) cells activate specific metabolic pathways to meet the increased energetic and biosynthetic demands associated with effector functions. Here, we foundin vivoactivation of NK cells duringListeria monocytogenesinfection-augmented transcription of genes encoding mitochondria-associated proteins in a manner dependent on the transcriptional coactivator PGC-1α. Using anNcr1Cre-based conditional knockout mouse, we found that PGC-1α was crucial for optimal NK cell effector functions and bioenergetics, as the deletion of PGC-1α was associated with decreased cytotoxic potential and cytokine production along with altered ADP/ATP ratios. Lack of PGC-1α also significantly impaired the ability of NK cells to control B16F10 tumor growthin vivo, and subsequent gene expression analysis showed that PGC-1α mediates transcription required to maintain mitochondrial activity within the tumor microenvironment. Together, these data suggest that PGC-1α-dependent transcription of specific target genes is required for optimal NK cell function during the response to infection or tumor growth.Graphical AbstractDisplay OmittedHighlights•NK cells activate mitochondria-associated gene transcription duringin vivochallenge•NK cell-specific deletion of PGC-1α results in energetic and functional defects•PGC-1α-deficient NK cells fail to clear B16F10 tumors to the level of WT cells•Reduced tumor clearance is associated with mitochondrial dysfunctionBiological Sciences; Cellular Physiology; Immunology; Cancer