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首页> 外文期刊>Cell metabolism >Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation
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Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation

机译:对调节和内存T细胞的戊唑氏酶作用与CPT1A介导的脂肪酸氧化无关

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摘要

T cell subsets including effector (Teff), regulatory (Treg), and memory (Tmem) cells are characterized by distinct metabolic profiles that influence their differentiation and function. Previous research suggests that engagement of long-chain fatty acid oxidation (LC-FAO) supports Foxp3+Tregcell and Tmemcell survival. However, evidence for this is mostly based on inhibition of Cpt1a, the rate-limiting enzyme for LC-FAO, with the drug etomoxir. Using genetic models to target Cpt1a specifically in T?cells, we dissected the role of LC-FAO in primary, memory, and regulatory T?cell responses. Here we show that the ACC2/Cpt1a axis is largely dispensable for Teff, Tmem, or Tregcell formation, and that the effects of etomoxir on T?cell differentiation and function are independent of Cpt1a expression. Together our data argue that metabolic pathways other than LC-FAO fuel Tmemor Tregdifferentiation and suggest alternative mechanisms for the effects of etomoxir that involve mitochondrial respiration.
机译:包括效应器(Teff),调节(Treg)和存储器(TMEM)单元的T细胞亚群的特征在于影响其分化和功能的不同代谢谱。以前的研究表明,长链脂肪酸氧化(LC-FAO)的参与支持Foxp3 + Tregcell和TMemcell存活率。然而,这主要是基于CPT1a的抑制,LC-FAO的速率限制酶,与药物Etomoxir。使用遗传模型特异性地在Tα细胞中靶向CPT1a,我们解释了LC-FAO在初级,记忆和调节T?细胞反应中的作用。在这里,我们表明ACC2 / CPT1A轴大大可用于Teff,TMEM或Tregcell形成,并且戊酮氧化对T 1的效果与CPT1A表达无关。我们的数据统一认为,除了LC-FAO燃料TMEMOR TMEMORING以外的代谢途径,并提出了依次抑制线粒体呼吸的替代毒素的效果的替代机制。

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