Can a Salty Diet Put You at Risk for Autoimmune Disease?

BWH researchers demonstrate a surprising connection between salt and autoimmune diseases. Kuchroo photo courtesy of Frank Siteman Photography.

Scientists Uncover a Connection, but More Research Needed

In a recent study, BWH researchers demonstrate a surprising connection between salt and autoimmune diseases. The researchers observed that salt influences susceptibility to autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and more.

The team, led by Vijay Kuchroo, DVM, PhD, co-director of the Infectious and Immunologic Diseases Center at BWH's Biomedical Research Institute and Samuel L. Wasserstrom Professor of Neurology in BWH's Department of Neurology, along with scientists from the Broad Institute, Harvard University and Yale University, tested the connection between salt and autoimmunity in pre-clinical and human models.

 Kuchroo and his team found that they could induce more severe forms of autoimmune diseases, and at higher rates, in mice fed a high-salt diet than in those that were fed a normal mouse diet.

Kuchroo notes however that the high-salt diet alone did not cause autoimmune diseases.

"It's not just salt, of course," said Kuchroo. "We have this genetic architecture-genes that have been tied to various forms of autoimmune diseases, and predispose a person to developing autoimmune diseases."  

Leading up to the Salt Discovery

Arriving at the salt discovery involved first understanding the genetic architecture and molecular growth of immune cells called Th17 cells. The researchers explored just exactly what the right activity levels of these cells should be-too little activity leaves a person vulnerable to foreign invaders like fungal infections, but too much activity can harm the body and lead to autoimmune diseases.

The researchers took 18 snapshots of developing Th17 cells to see what was happening inside them as they developed. Then, one-by-one, they ‘silenced' genes responsible for making these cells, using specially developed silicon nanowires to pierce the cells and delete key genes.

They discovered that Th17 cells were governed by two networks working in opposition to one another to both suppress and promote Th17 cell creation. One particular gene, known as SGK1, played an important role in the cells' development, and when turned off in mice, Th17 cells were not produced. SGK1 had not been observed in T cells before, but had been found in gut and kidney cells where it plays a role in absorbing salt.

Hence when the Kuchroo lab further explored this observation by feeding mice a high-salt diet, the presence of the SGK1 gene/protein in immune cells prompted a heightened response leading to autoimmune disease.  

 Next Steps

In spite of having discovered a salt-loving gene that is usually found in gut cells to also exist in and influence immune cell activity to a point where it induces severe forms of autoimmune diseases, the researchers note that there is still more to uncover and that they still need to directly test the impact of a high-salt diet on human autoimmune disease.

"We also suspect that environmental factors-infection, sunlight, smoking and vitamin D-may play a role. Salt could be one more thing on the list of predisposing environmental factors that may promote the development of autoimmunity," said Kuchroo.

Researchers caution that it is still premature to claim that people should not consume salt because it puts them at risk for autoimmune disease. The connection between salt and autoimmune disease needs to be further studied.

To view an interview with the researchers by the Broad Institute, visit http://youtu.be/t6lsucTFnB4.