Sodium chloride inhibits IFN‐γ, but not IL‐4, production by invariant NKT cells

Invariant NKT ( i NKT) cells are a distinct subset of T cells that exert Janus‐like functions in vivo by producing IFN‐γ and IL‐4. Sodium chloride modulates the functions of various immune cells, including conventional CD4 + T cells and macrophages. However, it is not known whether sodium chloride affects i NKT cell function, so we addressed this issue. Sodium chloride inhibited IFN‐γ, but not IL‐4, production by i NKT cells upon TCR or TCR‐independent (IL‐12 and IL‐18) stimulation in a dose‐dependent manner. Consistently, sodium chloride reduced the expression level of tbx21 , but not gata‐3 , in i NKT cells stimulated with TCR engagement or IL‐12 + IL‐18. Sodium chloride increased phosphorylated p38 expression in i NKT cells and inhibitors of p38, NFAT5, SGK1, and TCF‐1 restored IFN‐γ production by i NKT cells stimulated with sodium chloride and TCR engagement. Furthermore, adoptive transfer of i NKT cells pretreated with sodium chloride restored antibody‐induced joint inflammation to a lesser extent than for untreated i NKT cells in Jα18 knockout mice. These findings suggest that sodium chloride inhibits IFN‐γ production by i NKT cells in TCR‐dependent and TCR‐independent manners, which is dependent on p38, NFAT5, SGK1, and TCF‐1. These findings highlight the functional role of sodium chloride in i NKT cell‐mediated inflammatory diseases.