In three papers from Harvard and Yale Universities in the USA, published this week in the prestigious medical journal Nature, high salt concentrations have been linked to exacerbations of MS. It is known that the incidence of MS and autoimmunity in general is increasing and diet has long been thought to be one of the factors driving this change – especially dietary factors that have also rapidly changed such as the increased intake of processed foods with high salt content.
The researchers approached this by asking whether salt might have an effect on the immune cells that cause damage in MS, known as Th17 cells (click here for the abstract). In cells grown in the laboratory, the researchers increased the level of salt in the cellular environment so that it mimicked the levels that would be seen in a high salt diet. They found that increased levels of salt, or sodium chloride, caused precursor cells to develop into the damaging Th17 cells. The genetic signature of the salt-induced cells was stronger than normal Th17 cells, and indicated that the cells produced higher levels of signalling molecules important in producing autoimmunity.
The researchers then went on to look at the effects of a high salt diet in a laboratory model of MS. A high salt diet fed to the mice accelerated the onset and increased the severity of disease. Adding salt to their diets once they had disease also significantly worsened their symptoms. This was mediated by the stronger Th17 cells identified in the previous experiments.
In the accompanying paper (click here for the abstract), researchers used techniques to investigate the global genetic activity in precursor immune cells as they developed into the damaging Th17 cell type. Combined with computer modelling they have produced the first detailed map of how these cells are made. This information will lead to new target molecules for drugs, to try and switch off these cells in people with MS and other autoimmune disorders.
The third paper (click here for the abstract) also used an analysis of genetic activity to map the development of Th17 cells and identify the molecular triggers. This study showed that one of the major molecules in the development of Th17 cells, called SGK1, controls salt concentrations and transport within cells. They showed that only a modest increase in salt led to increased development of Th17 cells grown in the laboratory and increased numbers of these dangerous cells in animal models. In the reverse experiment, they showed that in animals without SGK1 disease was less frequent and considerably reduced. This was also the case when these mice were fed high salt diets – confirming SGK1 was the molecule responsible. SGK1 now represents an excellent target for future therapies.
While the authors are clear that it is not salt alone which causes MS, there are now plans to test the role of salt in clinical trials of people with autoimmune disorders that have a high Th17 component, such as MS or psoriasis, by giving them a very salt reduced diet. Since limiting salt is a relatively safe intervention, it is likely trials overseas will begin shortly.
MS Research Australia recommends people with MS consult with their healthcare practitioner prior to making any changes to their diet.