Elementary immunology: Na+ as a regulator of immunity

Abstract

The skin can serve as an interstitial Na⁺ reservoir. Local tissue Na⁺ accumulation increases with age, inflammation and infection. This increased local Na⁺ availability favors pro-inflammatory immune cell function and dampens their anti-inflammatory capacity. In this review, we summarize available data on how NaCl affects various immune cells. We particularly focus on how salt promotes pro-inflammatory macrophage and T cell function and simultaneously curtails their regulatory and anti-inflammatory potential. Overall, these findings demonstrate that local Na⁺ availability is a promising novel regulator of immunity. Hence, the modulation of tissue Na⁺ levels bears broad therapeutic potential: increasing local Na⁺ availability may help in treating infections, while lowering tissue Na⁺ levels may be used to treat, for example, autoimmune and cardiovascular diseases.

Keywords: Immune cell function and activation; Local Na+ availability; Macrophages; Skin salt storage; T cells.

Fig. 1

Effects of a high salt level on macrophage immunobiology. COX-2 Cyclooxygenase-2, NO nitric oxide, Nos2 type-2 NO synthase, TNF tumor necrosis factor, VEGF vascular endothelial growth factor

Fig. 2

Effects of a high salt level on T cell immunobiology. Fox01/3a Forkhead box O3 1/3a, IL-2 interleukin-2, NFAT5 nuclear factor of activated T cells, p38/MAPK p38/mitogen-activated protein kinase, SGK1 serum/glucocorticoid-regulated kinase 1