Dietary factors such as a high salt content can exert a potentially important influence on autoimmune disease. Two related papers by Hafler and Müller and colleagues in the Journal of Clinical Investigation demonstrate that elevated concentrations of NaCl can directly alter the function of both adaptive immunity and innate immunity. High concentrations of NaCl both in vitro and in vivo impair the function and generation of alternatively activated (M2) macrophages and the function of regulatory T cells (Treg cells). This perturbation seems to be unrelated to cell death or simple alterations in hypertonicity and instead requires activity of the kinase SGK1 in Treg cells and of SGK1 and the osmotically regulated transcription factor NFAT5 in M2 cells. However, high concentrations of NaCl do not result in increased polarization to inflammatory M1 cells. These papers demonstrate how dietary increases in NaCl can impair the suppressive activity of Treg cells and M2 cells and perturb their wound-healing function and together contribute to autoinflammatory disease.

J. Clin. Invest. (20 October 2015) doi:10.1172/JCI81151 & doi:10.1172/JCI80919