Fig. 2

Effects of high salt on the adaptive immune system. High concentration of salt increases the phosphorylation of the intracellular signaling molecule MAPK14 in the naïve CD4+ T cell, which also activates the transcription factor NFAT5. High salt also upregulates serum glucocorticoid-regulated kinase 1 (SGK1). Activated SGK1 phosphorylates forkhead box protein O-1 (FOXO1). Phosphorylated FOXO1 cannot bind to the IL-23 receptor (IL-23R) promoter which allows increased transcription of IL-23R as well as increased production of IL-23. Increased IL-23 level is a major stimulus for Th-17 cell differentiation. The phosphorylated FOXO1 protein also induces the expression of retinoic acid-receptor-related orphan receptor γt (RORγt), a transcription factor of Th17 cell differentiation Additionally, activated SGK1 and deactivated FOXO1 decrease the expression of FOXP3 which eventually reduces the differentiation of Treg cells. High salt also increases the INF-γ production from Treg cells, which decreases its suppressive activity