High Salt-Intake and Autoimmunity

The incidence of auto-immune diseases has dramatically increased in the past 50 years and the concern that environmental exposures have contributed to this increase is broadly suspected. However, it is very hard to pin-point to an individual factor. 

Very intriguing observations were just published at Nature linking a high-salt intake to increased auto-immunity. The authors demonstrate that a high-salt diet increased the severity of experimental autoimmune encephalomyelitis (*EAE) - a mouse model of multiple sclerosis . The authors proposed that high salt-intake induces serum glucocorticoid kinase 1 (SGK1), which than promotes IL-23R expression and enhances TH17 ** cell differentiation in vitro and in vivo. SGK1 has has been shown to govern Na transport and salt (NaCl) homeostasis in other cells. Mice lacking this kinase in their T cells have impaired expression of IL-17-family cytokines and of a receptor for another cytokine molecule, IL-23, which stabilizes the TH17 cell phenotype.

Though salt might not be the trigger of autoimmunity, the possibility that high-salt intake might exacerbate auto-immunity is very provoking and would encourage even more the emergent initiation of trials evaluating the efficacy of low salt-diet in the development of auto-immune diseases and other potential diseases related to inflammation, such as coronary heart disease. 

Based on recent computer-generated data suggesting all the potential benefits of lowering salt consumption, this discussion is very pertinent.  

Above the diagram from the Editorial of Nature discussing the findings and below some additional explanations about the mouse model and Th17 cells. One caveat is that effect of high sodium on human cells was only shown in vitro...

* EAE: Experimental autoimmune encephalomyelitis. An animal model of the human autoimmune disease multiple sclerosis. EAE is experimentally induced in animals by immunization with myelin or with peptides derived from myelin. The animals develop a paralytic disease with inflammation and demyelination in the brain and spinal cord.

** TH17 cells (T helper 17 cells). A subset of CD4+ T helper cells that produce interleukin-17 (IL-17) and that are thought to be important in inflammatory and autoimmune diseases. Their generation involves IL-6, IL-21 and IL-23, as well as the transcription factors RORgt (retinoic-acid-receptor-related orphan receptor-gt) and STAT3 (signal transducer and activator of transcription 3).