High salt induces pathogenic Th17 cells and exacerbates autoimmune diseases (60.13)

Abstract Interleukin (IL)-17 producing CD4+ helper T cells (Th17 cells) play a pivotal role in autoimmune diseases. Apart from their importance for the control of certain pathogens, IL-23 dependent Th17 cells have been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE). Moreover, genetic risk factors associated with multiple sclerosis (MS) are linked to the IL23/Th17 pathway. Besides genetic factors, the increased incidence of autoimmune diseases like MS in developed countries is also believed to be related to environmental risk factors. However, how environmental risk factors such as changes in diet, sun exposure or medications could directly influence the development of pathogenic Th17 cells is not well established. Here we show that increased salt (sodium chloride; NaCl) concentrations dramatically boost the induction of murine and human Th17 cells in vitro. Moreover, mice fed with a high salt diet develop a very severe form of EAE, dependent on the induction of highly pathogenic Th17 cells. The generation of Th17 cells under high salt conditions is well regulated on the molecular level and seems to be dependent on specific pathways. Thus, increased salt intake, which may represents one of the biggest contributors to changes in diet during the last half century and accounts for cardiovascular disease, might also represent an environmental risk factor for autoimmune diseases through the exacerbated induction of pathogenic Th17 cells.