New discovery reveals role of salt in autoimmune disease mechanisms

Researchers at the US Yale University have uncovered a protein linked to the loss of immune regulation in autoimmune diseases like multiple sclerosis in a recent breakthrough highlighted by SciTechDaily.

Researchers at Yale have discovered a protein that plays a key role in the loss of immune regulation linked to multiple sclerosis and other autoimmune diseases. This breakthrough, which underscores the influence of environmental factors such as high salt intake, points to a new avenue for creating broad-spectrum treatments for autoimmune conditions. 

New Advances in Autoimmune Research Over 20 years ago, David Hafler’s research team at Harvard identified a type of T cell that helps regulate the immune system. They later linked dysfunction in these regulatory T cells to autoimmune diseases like multiple sclerosis (MS). However, the exact mechanism behind this dysfunction has been elusive until now. A recent study led by Yale researchers, including Tomokazu Sumida, assistant professor at Yale School of Medicine, and Hafler, now a professor at Yale, has uncovered that an increase in the protein PRDM1-S is responsible for the loss of immune regulation.

This finding reveals a complex interplay of genetic and environmental factors, such as high salt intake, affecting immune function. Published on August 28 in Science Translational Medicine, these results highlight a new potential target for universal treatments for autoimmune diseases. Unveiling the Mechanism of MS “These experiments reveal a key underlying mechanism for the loss of immune regulation in MS and likely other autoimmune diseases,” said Hafler, who is also chair of Yale’s Department of Neurology. “They also add mechanistic insight into how Treg [regulatory T cells] dysfunction occurs in human autoimmune diseases.” 

Autoimmune diseases, prevalent among young adults, are influenced by both genetic and environmental factors such as vitamin D deficiency and fatty acid imbalances. In previous research, Sumida and Hafler discovered that high salt intake contributes to multiple sclerosis (MS) by inducing inflammation in CD4 T cells and impairing regulatory T cell function. This effect was linked to the salt-sensitive enzyme SGK-1, crucial for cell signaling. In their latest study, the researchers employed RNA sequencing to compare gene expression between MS patients and healthy individuals. They found that patients with MS exhibited elevated levels of PRDM1-S (also known as BLIMP-1), a gene involved in immune regulation.

The study revealed that PRDM1-S increases the expression of the salt-sensitive SGK-1 enzyme, which disrupts regulatory T cells. This overexpression of PRDM1-S was also observed in other autoimmune diseases, suggesting it might be a widespread marker of regulatory T cell dysfunction. "With these findings, we are now working on developing drugs to target and reduce PRDM1-S expression in regulatory T cells," Sumida noted. 

"We are also collaborating with other Yale researchers and employing advanced computational methods to enhance regulatory T cell function and create new treatments for various autoimmune diseases." The research was conducted in collaboration with Bradley Bernstein and Manolis Kellis from the Broad Institute of MIT and Harvard, along with several other institutions. Yale lab contributors included neurologist Matthew R. Lincoln, and research assistants Alice Yi, Helen Stillwell, and Greta Leissa.