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

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.

Keywords: AMPK; Atherosclerosis; CD4+ T cell; Immunometabolism; mTOR.