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Complex Interplay Between Metabolism and CD4+ T-Cell Activation, Differentiation, and Function: a Novel Perspective for Atherosclerosis Immunotherapy

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Abstract

Atherosclerosis is a complex pathological process that results from the chronic inflammatory reaction of the blood vessel wall and involves various immune cells and cytokines. An imbalance in the proportion and function of the effector CD4+ T-cell (Teff) and regulatory T-cell (Treg) subsets is an important cause of the occurrence and development of atherosclerotic plaques. Teff cells depend on glycolytic metabolism and glutamine catabolic metabolism for energy, while Treg cells mainly rely on fatty acid oxidation (FAO), which is crucial for determining the fate of CD4+ T cells during differentiation and maintaining their respective immune functions. Here, we review recent research achievements in the field of immunometabolism related to CD4+ T cells, focusing on the cellular metabolic pathways and metabolic reprogramming involved in the activation, proliferation, and differentiation of CD4+ T cells. Subsequently, we discuss the important roles of mTOR and AMPK signaling in regulating CD4+ T-cell differentiation. Finally, we evaluated the links between CD4+ T-cell metabolism and atherosclerosis, highlighting the potential of targeted modulation of CD4+ T-cell metabolism in the prevention and treatment of atherosclerosis in the future.

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This work was supported by the National Natural Scientific Fund of China (No. 81871858), the Fundamental Research Funds for the Central Universities of Central South University, and the Hunan Provincial Innovation Foundation for Postgraduates (No. CX20220325).

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  1. Department of Cardiology, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, 410000, Hunan, China

    Jingmin Yang, Yanying Chen, Xiao Li, Huali Qin, Jinghui Bao, Chunfang Wang, Xiaochen Dong & Danyan Xu

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Danyan Xu and Jingmin Yang conceived of the scope of the review and revised the manuscript. Jingmin Yang was involved in the collection of the relevant references and drafted the manuscript. Other authors helped revise and provide many valuable comments about the manuscript. All authors read and approved the final manuscript.

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Yang, J., Chen, Y., Li, X. et al. Complex Interplay Between Metabolism and CD4+ T-Cell Activation, Differentiation, and Function: a Novel Perspective for Atherosclerosis Immunotherapy. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07466-9

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