Regulation of T cell immunity by cellular metabolism

doi:10.1007/s11684-018-0668-2

Front. Med.

2018, Vol. 12

Issue (4) : 463-472 https://doi.org/10.1007/s11684-018-0668-2

REVIEW

Regulation of T cell immunity by cellular metabolism

Zhilin Hu, Qiang Zou(

), Bing Su(

)

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

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Abstract

T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.

Keywords T cell immunity metabolic pathways nutrient uptake metabolic checkpoints

Corresponding Author(s): Qiang Zou,Bing Su

Just Accepted Date: 25 July 2018 Online First Date: 10 August 2018 Issue Date: 03 September 2018

Cite this article:

Zhilin Hu,Qiang Zou,Bing Su. Regulation of T cell immunity by cellular metabolism[J]. Front. Med., 2018, 12(4): 463-472.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0668-2
https://academic.hep.com.cn/fmd/EN/Y2018/V12/I4/463

Fig.1 Metabolic regulation of the T cell life cycle. The energy demands of naïve T cells mainly come from oxidative phosphorylation (OXPHOS). After T cell receptor (TCR) stimulation, the naïve T cells differentiate into antigen-effector T cells, whose energy metabolism mainly depends on aerobic glycolysis and OXPHOS. Glycolytic metabolism distinguishes CD4 Th1, Th2, and Th17 effector cells from regulatory T cells (Treg). The development of Treg and memory T cells (Tmem) mainly depends on fatty acid oxidation (FAO) and catabolism. Membrane T cells reenter the resting state, and their energy metabolism depends on OXPHOS.

Fig.2 Simplified scheme of T cell metabolism regulated by mTOR signaling. TCR and CD28 signals induce the expression of metabolism-related genes, such as glucose transporter Glut1 (murine gene name Slc2a1), and increase the glucose uptake of T cells. Then, glucose is degraded by glycolysis to generate pyruvate molecules, lactate, or acetyl-CoA. Acetyl-CoA is required for the tricarboxylic acid (TCA) cycle and utilized as a precursor of fatty acid synthesis (FAS). TCR and CD28 stimulation also induces AKT phosphorylation via PDK1 and mTORC2 and promotes mTORC1 activation, leading to the elevated glycolysis and increased levels of pyruvate molecules. By contrast, AMPK promotes FAO and inhibits FAS by negatively regulating ACC1/2. AMPK can inhibit mTOR activity to downregulate glycolysis. Therefore, mTOR and AMPK act as negative regulators for each other.

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Heng Fang, Aihua Zhang, Xiaohang Zhou, Jingbo Yu, Qi Song, Xijun Wang. High-throughput metabolomics reveals the perturbed metabolic pathways and biomarkers of Yang Huang syndrome as potential targets for evaluating the therapeutic effects and mechanism of geniposide[J]. Front. Med., 2020, 14(5): 651-663.

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