High-salt diet suppresses autoimmune demyelination by regulating the blood-brain barrier permeability.

Abstract

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 T_H17 cell differentiation [M. Kleinewietfeld <i>et al.</i>, <i>Nature</i> 496, 518-522 (2013); C. Wu <i>et al.</i>, <i>Nature</i> 496, 513-517 (2013); N. Wilck <i>et al.</i>, <i>Nature</i> 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.