A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives.

Zhongyu Han,Linjiang Song,Xiyalatu Sai,Chi Liu,Hongxia Tao,Qing Nian,Kuai Ma,Hongli Liu,Mingxuan Chi,Yunlong Li,Jiong Zhang

doi:10.3389/fimmu.2022.826732

Abstract

Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

Highlights

The kidney is an important organ for excreting metabolic waste and maintaining internal environmental stability and plays an extremely important role in metabolic activities [1] (Figure 1)
We summarized some drugs that target metabolic pathways; for example, 2-deoxy-d-glucose (2-DG), a drug that can compete with glucose in binding to hexokinase II (HKII) to inhibit cellular glycolysis activity and regulate the glycolytic pathway, induces Treg cell differentiation and suppression and alleviates the progression of systemic lupus erythematosus (SLE)
Mitochondrial dysfunction is one of the important characteristics of Acute kidney injury (AKI) [239]; the accumulation of cytochrome C in the mitochondria causes the oxidative respiratory chain to fail to proceed normally, and mitochondrial respiration is weakened, which further affects the metabolism of lactic acid in the kidney tissue, causing metabolic acidosis [240]

Summary

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease

Zhongyu Han 1,2,3†, Kuai Ma 4†, Hongxia Tao 3†, Hongli Liu 3, Jiong Zhang 1,2, Xiyalatu Sai 5, Yunlong Li 3, Mingxuan Chi 1,2, Qing Nian 2,6*, Linjiang Song 3* and Chi Liu 1,2*. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells.

INTRODUCTION

Findings

CONCLUSION