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

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.

CD4+ T-cell subsets in autoimmune hepatitis: A review

“…Treg cells are important immunosuppressive cells, which are divided into tTregs and peripheral-induced Treg cells according to their origin. 120 tTregs mature after positive and negative selection in the thymus and can be enriched by TCRs that recognize self-antigens; peripheral-induced Treg cells can be differentiated from Th0 cells on exposure to IL-2 and TGF-β. 121 Treg cells have been identified as CD4 + CD25 + Foxp3 + T cells, and Foxp3 is a key transcription factor.…”

Identification of biomarkers for the diagnosis of chronic kidney disease (CKD) with non-alcoholic fatty liver disease (NAFLD) by bioinformatics analysis and machine learning

“…There is some evidence to suggest that Tregs cells can inhibit inflammation and fibrosis in CKD (47). In turn, the CKD microenvironment changes the energetic metabolism of Tregs cells, thus inhibiting the protective effect of Tregs (48). Therefore, immune cells interact with the inflammatory microenvironment.…”

The role of N6-methyladenosine (m6A) in kidney diseases

“…For example, macrophages clear pathogens and cellular debris, while dendritic cells uptake and present antigens to activate lymphocytes. T cells collaborate with other immune cells to generate cytokines that protect the kidney and preserve its intrarenal environment (56). Systemic immunological and autoimmune illnesses, such as complement diseases, immune complex-related seropathies, systemic autoimmunity, and vasculitis, frequently target the kidney, causing significant renal damage (57).…”

“…In a normal steady-state environment, various innate and adaptive immune cells reside in the kidney, including dendritic cells, mast cells, macrophages, natural killer cells, NKT (natural killer T) cells, T cells, and B cells ( Figure 3 ). These cells carry out essential functions to maintain renal homeostasis ( 56 ).…”

“…For example, macrophages clear pathogens and cellular debris, while dendritic cells uptake and present antigens to activate lymphocytes. T cells collaborate with other immune cells to generate cytokines that protect the kidney and preserve its intrarenal environment ( 56 ).…”