CD4+ T-cell differentiation and function: Unifying glycolysis, fatty acid oxidation, polyamines NAD mitochondria
CD4+ T-cell differentiation and function: Unifying glycolysis, fatty acid oxidation, polyamines NAD mitochondria
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DOI：
10.1016/j.jaci.2021.03.033
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发表时间：
2021-07-05
影响因子：
14.2
通讯作者：
Sparwasser, Tim
中科院分区：
文献类型：
--
作者：
Almeida, Luis;Dhillon-LaBrooy, Ayesha;Sparwasser, Tim
通过T细胞发育、活化和效应子功能的不同步骤的进展与特定的细胞代谢过程紧密结合。以前的研究表明，T效应细胞具有有氧糖酵解的代谢偏好，而初始和调节性T细胞主要依赖于氧化磷酸化。最近，免疫代谢领域已经偏离了线粒体代谢在T细胞活化和功能中几乎不重要的概念。值得注意的是，T细胞具有代谢混杂性，这使得它们能够根据组织环境来适应其营养需求。总而言之，这些代谢途径的整合不仅产生能量，而且产生中间产物，这些中间产物可以调节表观遗传程序，导致T细胞命运的变化。在这篇综述中，我们讨论了糖酵解，氨基酸催化剂，脂肪酸氧化如何与三羧酸循环一起工作的最新文献。我们还强调了电子传递链对T细胞免疫的重要性。我们还讨论了新的发现，强调了关键酶，辅助途径和翻译后蛋白修饰的作用，这些修饰独特地调节T细胞功能，并可能代表治疗目的的突出候选者。nbsp;你好
The progression through different steps of T-cell development, activation, and effector function is tightly bound to specific cellular metabolic processes. Previous studies established that T-effector cells have a metabolic bias toward aerobic glycolysis, whereas naive and regulatory T cells mainly rely on oxidative phosphorylation. More recently, the field of immunometabolism has drifted away from the notion that mitochondrial metabolism holds little importance in T-cell activation and function. Of note, T cells possess metabolic promiscuity, which allows them to adapt their nutritional requirements according to the tissue environment. Altogether, the integration of these metabolic pathways culminates in the generation of not only energy but also intermediates, which can regulate epigenetic programs, leading to changes in T-cell fate. In this review, we discuss the recent literature on how glycolysis, amino acid catabolism, and fatty acid oxidation work together with the tricarboxylic acid cycle in the mitochondrion. We also emphasize the importance of the electron transport chain for T-cell immunity. We also discuss novel findings highlighting the role of key enzymes, accessory pathways, and posttranslational protein modifications that distinctively regulate T-cell function and might represent prominent candidates for therapeutic purposes.& nbsp;