LAUSR

Significance Dietary salt intake has been considered an important risk factor for autoimmune diseases like multiple sclerosis (MS). Here we studied the effects of a high-salt diet (HSD) using a spontaneous autoimmune disease mouse model resembling MS. We found that high-salt consumption protects mice from developing the neurological disease by promoting the tightening of the blood–brain barrier and preventing the migration of autoreactive T cells into the CNS. Our results emphasize the multifarious effects of high-salt consumption in autoimmune disease susceptibility. Sodium chloride, “salt,” is an essential component of daily food and vitally contributes to the body’s homeostasis. However, excessive salt intake has often been held responsible for numerous health risks associated with the cardiovascular system and kidney. Recent reports linked a high-salt diet (HSD) to the exacerbation of artificially induced central nervous system (CNS) autoimmune pathology through changes in microbiota and enhanced TH17 cell differentiation [M. Kleinewietfeld et al., Nature 496, 518–522 (2013); C. Wu et al., Nature 496, 513–517 (2013); N. Wilck et al., Nature 551, 585–589 (2017)]. However, there is no evidence that dietary salt promotes or worsens a spontaneous autoimmune disease. Here we show that HSD suppresses autoimmune disease development in a mouse model of spontaneous CNS autoimmunity. We found that HSD consumption increased the circulating serum levels of the glucocorticoid hormone corticosterone. Corticosterone enhanced the expression of tight junction molecules on the brain endothelial cells and promoted the tightening of the blood–brain barrier (BBB) thereby controlling the entry of inflammatory T cells into the CNS. Our results demonstrate the multifaceted and potentially beneficial effects of moderately increased salt consumption in CNS autoimmunity.