Salt a possible trigger for autoimmune diseases

Salt has been blamed for a host of health problems in recent years, including hypertension, osteoporosis, stomach cancer and stroke. Now, Yale researchers are suggesting salt may have a role in the increased incidence of autoimmune diseases such as multiple sclerosis (MS).

In the 6 March issue of the journal Nature, Yale researchers showed that salt can induce and worsen pathogenic immune-system responses in mice. The response is regulated by genes already implicated in a variety of autoimmune diseases.

In accompanying papers in the same issue of Nature, researchers from Brigham and Women’s Hospital and Harvard identified the key molecular pathway involved in the response to salt, and the Broad Institute sketched out the regulatory network of genes that governs this autoimmune response.

“These are not diseases of bad genes alone or diseases caused by the environment, but diseases of a bad interaction between genes and the environment,” said Dr David Hafler, senior author of the Yale paper.

The research was inspired, in part, by an observation that eating at fast-food restaurants tended to trigger an increase in production of inflammatory cells, which are mobilised by the immune system to respond to injury or pathogens but which, in autoimmune diseases, attack healthy tissue. Researchers led by Dominik Mueller wanted to know whether high salt content in diet might induce the destructive immune system response that is the hallmark of autoimmunity.

They found that adding salt to the diet of mice induced production of a type of T cells previously associated with autoimmune diseases and that mice on salt diets developed a more severe form of an MS animal model, experimental autoimmune encephalomyelitis.

The research expands the understanding of how one type of immune cell - known as a T helper 17 or Th17 cell - develops, and how its growth influences the development of other kinds of cells involved in the immune system. Reconstruction of this molecular circuitry confirmed the surprising role of salt, said the researchers.

“The question we wanted to pursue was: how does this highly pathogenic, pro-inflammatory T cell develop?” said Vijay Kuchroo, Wasserstrom Professor of Neurology at Harvard Medical School and co-director of the Center for Infection and Immunity at Biomedical Research Institutes. “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.”

“Humans were genetically selected for conditions in sub-Saharan Africa, where there was no salt,” Hafler said. “Today, Western diets all have high salt content and that has led to increase in hypertension and perhaps autoimmune disease as well.”

Hafler noted that all test-tube cell biology is performed based on the salt levels found in blood and not in the tissues where immune cell ultimately travel to fight infections. That may have been a reason salt’s role in autoimmunity has gone undetected.

Patient trials to assess effects of salt on autoimmune diseases are being planned.

Hafler is not waiting with his own patients. “I already recommend that my patients use a low-salt, low-fat diet,” he said.