Reporting in the journal Nature, the researchers said high-salt diets increased levels of a type of immune cell linked with autoimmune disease. And mice genetically engineered to develop multiple sclerosis (MS) got much worse when they ate what amounted to a high-salt Western diet compared with mice who had more moderate salt intake.
The findings suggest that salt may play a previously unknown role in triggering autoimmune diseases such as MS or type 1 diabetes in individuals who are already genetically predisposed.
"It's not bad genes. It's not bad environment. It's a bad interaction between genes and the environment," said Dr. David Hafler, a professor of immunobiology at Yale University in New Haven, Connecticut, and senior author of one of the three papers.
High salt intake is already a known culprit in increasing the risk of heart disease and hypertension. The new study now implicates high-salt diets in increasing rates of autoimmune disease. "It can't be just salt. We know vitamin D probably plays a small component. We know smoking is a risk factor. This now suggests that salt is also a risk factor," Hafler said.
"How much? We don't know," he added.
Hafler became interested in studying the link between salt and autoimmunity through studies of the gut microbiome - a census of gut microbes and cell function of 100 healthy individuals.
The team noticed that when people in the study visited fast food restaurants more than once a week, they saw a marked increase in levels of destructive inflammatory cells, which the immune system produces to respond to injury or foreign invaders, but which attack healthy tissues in autoimmune diseases.
He shared these findings with colleagues at Harvard Medical School and the Broad Institute of Harvard and the Massachusetts Institute of Technology and others who were working out what factors induce the activity of a type of autoimmune cell known as a T helper 17 or a Th17 cell.
Th17 cells can promote inflammation that is important for defending against pathogens, but they have also been linked to diseases like multiple sclerosis, psoriasis, rheumatoid arthritis, and ankylosing spondylitis. Treatment options for some of these diseases, such as psoriasis, include manipulating T cell function.
"The question we wanted to pursue was: How does this highly pathogenic, pro-inflammatory T cell develop?" said Vijay Kuchroo of the Harvard-affiliated Brigham and Women's Hospital and a member of the Broad Institute.
"Once we have a more nuanced understanding of the development of the pathogenic Th17 cells, we may be able to pursue ways to regulate them or their function."
Hafler said Kuchroo's team worked on tracing how these immune cells were wired, and what triggered their development. They identified a specific gene known as SGK1 that plays an important role in the cells' development. This gene had not been seen in T cells before, but it has been known to play a role in absorbing salt in the gut and kidneys.
"We put the two together and went after this," Hafler said.
Researchers at Harvard and Yale and colleagues in Germany led by Dominik Mueller looked to see whether a high-salt diet could induce the destructive immune system response that is the hallmark of autoimmunity.
They found that adding salt to the diet of mice induced the production of Th17 cells and that mice genetically engineered to develop a form of MS had more severe disease than mice fed a normal mouse diet.
Hafler says the findings now need to be studied in people. He has already gotten permission to test the effects of lowering the salt intake in the diets of individuals with multiple sclerosis to see if their symptoms improve.
It likely be years before this link is confirmed, but Hafler says for patients already at risk of autoimmune disease, reducing dietary salt may be a good idea.
"If I had MS, I would think very much about not eating processed foods and really cutting down my salt intake," he said.