葡萄糖转运体GLUT3通过糖酵解-表观重编程控制T辅助17细胞反应
2022-03-27   阅读:493   来源:细胞

德国维尔茨堡大学Martin Vaeth团队发现,葡萄糖转运体GLUT3通过糖酵解-表观重编程控制T辅助17细胞反应。2022年3月21日,国际知名学术期刊《细胞—代谢》在线发表了这一成果。

研究人员表明,糖酵解的重新编程还能通过表观遗传重塑控制炎症基因的表达。研究人员发现,葡萄糖转运体GLUT3对自身免疫性结肠炎和脑脊髓炎模型中Th17细胞的效应功能至关重要。在分子水平上,结果表明GLUT3依赖性的葡萄糖摄取控制着一个代谢-转录回路,该回路调节着Th17细胞的致病性。代谢组、表观遗传学和转录组分析将GLUT3与线粒体葡萄糖氧化和ACLY依赖的乙酰CoA生成联系起来,这些是表观遗传学调节炎症基因表达的限速步骤。这些发现从转化的角度来看也很重要,因为抑制GLUT3依赖的乙酰CoA生成是一个有希望的代谢检查点,可用于减轻Th17细胞介导的炎症性疾病。

据悉,代谢重编程是活化T细胞的一个标志。从氧化磷酸化到有氧糖酵解的转换,为大分子的生物合成提供了能量和中间代谢物,从而支持克隆扩增和效应功能。

附:英文原文

Title: The glucose transporter GLUT3 controls T helper 17 cell responses through glycolytic-epigenetic reprogramming

Author: Sophia M. Hochrein, Hao Wu, Miriam Eckstein, Laura Arrigoni, Josip S. Herman, Fabian Schumacher, Christian Gerecke, Mathias Rosenfeldt, Dominic Grün, Burkhard Kleuser, Georg Gasteiger, Wolfgang Kastenmüller, Bart Ghesquière, Jan Van den Bossche, E. Dale Abel, Martin Vaeth

Issue&Volume: 2022-03-21

Abstract: Metabolic reprogramming is a hallmark of activated T cells. The switch from oxidativephosphorylation to aerobic glycolysis provides energy and intermediary metabolitesfor the biosynthesis of macromolecules to support clonal expansion and effector function.Here, we show that glycolytic reprogramming additionally controls inflammatory geneexpression via epigenetic remodeling. We found that the glucose transporter GLUT3is essential for the effector functions of Th17 cells in models of autoimmune colitisand encephalomyelitis. At the molecular level, we show that GLUT3-dependent glucoseuptake controls a metabolic-transcriptional circuit that regulates the pathogenicityof Th17 cells. Metabolomic, epigenetic, and transcriptomic analyses linked GLUT3 tomitochondrial glucose oxidation and ACLY-dependent acetyl-CoA generation as a rate-limitingstep in the epigenetic regulation of inflammatory gene expression. Our findings arealso important from a translational perspective because inhibiting GLUT3-dependentacetyl-CoA generation is a promising metabolic checkpoint to mitigate Th17-cell-mediatedinflammatory diseases.

DOI: 10.1016/j.cmet.2022.02.015

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