The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival.
The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival.
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DOI：
10.3389/fimmu.2017.01949
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发表时间：
2017
影响因子：
7.3
通讯作者：
Waldmann H
中科院分区：
文献类型：
--
作者：
Howie D;Ten Bokum A;Necula AS;Cobbold SP;Waldmann H
先天免疫系统和获得性免疫系统的分化和效应器功能都与细胞新陈代谢密不可分。影响免疫系统两臂的代谢特征包括代谢底物的可用性，控制这些底物分解代谢的酶、运输蛋白和转录因子的表达，以及执行合成代谢的能力。脂质代谢的控制对T淋巴细胞的适当分化和功能至关重要，最终也是维持免疫耐受的关键。这篇综述将集中于脂肪酸代谢在T细胞分化、效应功能和生存中的作用。Fas是细胞能量的重要来源，以甘油三酯的形式储存。它们也被用作生产复杂脂质的前体，如胆固醇和膜磷脂。FA残留物也会被合并到激素和信号部分中。Fas信号通过核受体及其通道，在作为三酰甘油储存或作为燃料的氧化之间，可能在细胞的生存或死亡中发挥作用。近年来，免疫代谢领域的进展突显了FA代谢在CD4和CD8T细胞分化和功能中的不同作用。这篇综述将首先描述环境FAs和细胞内脂质信号的感知和调节，然后将探讨脂质代谢在调节潜在的破坏性促炎和抗炎调节反应之间的关键作用。最后，我们将讨论细胞外FAs在决定细胞存活中的复杂作用。
The differentiation and effector functions of both the innate and adaptive immune system are inextricably linked to cellular metabolism. The features of metabolism which affect both arms of the immune system include metabolic substrate availability, expression of enzymes, transport proteins, and transcription factors which control catabolism of these substrates, and the ability to perform anabolic metabolism. The control of lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes, and ultimately to the maintenance of immune tolerance. This review will focus on the role of fatty acid (FA) metabolism in T cell differentiation, effector function, and survival. FAs are important sources of cellular energy, stored as triglycerides. They are also used as precursors to produce complex lipids such as cholesterol and membrane phospholipids. FA residues also become incorporated into hormones and signaling moieties. FAs signal via nuclear receptors and their channeling, between storage as triacyl glycerides or oxidation as fuel, may play a role in survival or death of the cell. In recent years, progress in the field of immunometabolism has highlighted diverse roles for FA metabolism in CD4 and CD8 T cell differentiation and function. This review will firstly describe the sensing and modulation of the environmental FAs and lipid intracellular signaling and will then explore the key role of lipid metabolism in regulating the balance between potentially damaging pro-inflammatory and anti-inflammatory regulatory responses. Finally the complex role of extracellular FAs in determining cell survival will be discussed.