Immunometabolism of regulatory T cells

Abstract

The bidirectional interaction between the immune system and whole-body metabolism has been well recognized for many years. Via effects on adipocytes and hepatocytes, immune cells can modulate whole-body metabolism (in metabolic syndromes such as type 2 diabetes and obesity) and, reciprocally, host nutrition and commensal-microbiota-derived metabolites modulate immunological homeostasis. Studies demonstrating the metabolic similarities of proliferating immune cells and cancer cells have helped give birth to the new field of immunometabolism, which focuses on how the cell-intrinsic metabolic properties of lymphocytes and macrophages can themselves dictate the fate and function of the cells and eventually shape an immune response. We focus on this aspect here, particularly as it relates to regulatory T cells.

HIF1α and metabolic reprogramming in inflammation

“…Silencing of HIF1α in Tregs reverses these proinflammatory effects and restores their regulatory function (78). This direct modulation of the TH17/Treg balance marks HIF1α as an important director of T cell fate and immune effector functions (22,79).…”

Insight into the Glucose Metabolism of Immune Cells in Sepsis

“…During recent years, a growing number of studies have shown the importance of metabolic signals in immunity, the cellular metabolism dictates the fate and function of the immune cells (17)(18)(19)(20). To seek an effective treatment for sepsis, it will be helpful to elucidate metabolic process in the immune cells and analyze their metabolic changes in sepsis (20).…”

“…Following pathogen invasion, the innate immune cells and T cells are activated and generate energy and essential components used in biosynthesis by switching metabolism from oxidative phosphorylation to aerobic glycolysis which is similar to the Warburg effect of tumor cells ( Figure 2) (18,21). Lipopolysaccharide (LPS) stimulation leads to an increase in the glycolytic process, while a decrease in mitochondria-dependent pyruvate oxidation and glutamine consumption, and fatty acid β-oxidation in monocytes/macrophages (22,23).…”

“…Lipopolysaccharide (LPS) stimulation leads to an increase in the glycolytic process, while a decrease in mitochondria-dependent pyruvate oxidation and glutamine consumption, and fatty acid β-oxidation in monocytes/macrophages (22,23). Furthermore, inhibition of mTOR or deletion of HIF-1α dampens the metabolic change induced by danger signals, which indicates that this metabolic change of immune cells is also mainly regulated by protein kinase B (Akt)-mammalian target of rapamycin (mTOR)-hypoxia inducible factor (HIF)-1α pathway (18,(22)(23)(24) (Figure 3). Considering activated immune cells and tumor cells share similar signaling pathway of the metabolic switch, it is reasonable to infer that we can learn from the experiences of the strategies for the prevention and treatment of cancer.…”

Cytokines and Metabolic Factors Regulate Tumoricidal T-Cell Function During Cancer Immunotherapy

“…An emerging example is the rise in obesity and its connection to T-cell biology [37], especially Tregs [38]. While obesity is a risk factor for a broad range of metabolic disorders, 3.6% of all new cancer cases worldwide are attributable to obesity [39].…”