High-salt modulates cellular metabolism of human regulatory T cells

Abstract High-salt intake has been linked with shifts in the immune cell balance, mainly by promoting proliferation and activity of pro-inflammatory cells, such as T helper 17 (Th17) and M1 macrophages, and by impairing the functions of anti-inflammatory cells such as regulatory T cells (Tregs) and M2 macrophages. However, the precise molecular mechanisms that contribute to this phenomenon are still unknown. The role of metabolic regulation in shaping immune responses has gained increasing attention in recent years and can be greatly influenced by environmental factors such as diet. High-salt intake was previously shown to promote metabolic changes in M2 macrophages by decreasing their mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis necessary for their activation. So we hypothesize that this phenomenon could likely be extrapolated to other cell types such as Tregs. We analyzed changes on the metabolic pathways of human Tregs after high-salt exposure. Our results show significant salt-induced changes in the cellular metabolism of Tregs and since these changes are known to alter suppressive function both in vitro and in vivo, we further hypothesize that the observed metabolic alterations might be linked to the loss of suppressive function seen in human Tregs upon high-salt challenge. Thus, the interference with these pathways may have the potential for targeting Tregs in salt-sensitive diseases.