This study investigates the role of sodium chloride (NaCl) in the induction of pathogenic Th17 cells, which are crucial in autoimmune diseases. The authors found that increased NaCl concentrations, similar to those found in physiological conditions, significantly enhance the induction of murine and human Th17 cells. This effect is mediated through the activation of the p38/MAPK pathway, involving the tonicity-responsive enhancer binding protein (TonEBP/NFAT5) and the serum/glucocorticoid-regulated kinase 1 (SGK1). Gene silencing or chemical inhibition of these pathways abrogates the high-salt-induced Th17 cell development. Th17 cells generated under high-salt conditions exhibit a highly pathogenic and stable phenotype, characterized by up-regulation of pro-inflammatory cytokines such as GM-CSF, TNFα, and IL-2. Additionally, mice fed a high-salt diet develop a more severe form of experimental autoimmune encephalomyelitis (EAE), indicating that increased dietary salt intake might be an environmental risk factor for autoimmune diseases. The study suggests that dietary salt intake could be a significant environmental factor contributing to the increasing incidence of autoimmune diseases, particularly multiple sclerosis (MS) and type 1 diabetes.This study investigates the role of sodium chloride (NaCl) in the induction of pathogenic Th17 cells, which are crucial in autoimmune diseases. The authors found that increased NaCl concentrations, similar to those found in physiological conditions, significantly enhance the induction of murine and human Th17 cells. This effect is mediated through the activation of the p38/MAPK pathway, involving the tonicity-responsive enhancer binding protein (TonEBP/NFAT5) and the serum/glucocorticoid-regulated kinase 1 (SGK1). Gene silencing or chemical inhibition of these pathways abrogates the high-salt-induced Th17 cell development. Th17 cells generated under high-salt conditions exhibit a highly pathogenic and stable phenotype, characterized by up-regulation of pro-inflammatory cytokines such as GM-CSF, TNFα, and IL-2. Additionally, mice fed a high-salt diet develop a more severe form of experimental autoimmune encephalomyelitis (EAE), indicating that increased dietary salt intake might be an environmental risk factor for autoimmune diseases. The study suggests that dietary salt intake could be a significant environmental factor contributing to the increasing incidence of autoimmune diseases, particularly multiple sclerosis (MS) and type 1 diabetes.