In a new study, a team of researchers found the loss of immune regulation, linked to diseases such as multiple sclerosis, is triggered by an increase in PRDM1-S,a protein involved in immune function, triggering a dynamic interaction of multiple genetic and environmental factors, including high salt uptake.  The findings reveal a new target for a universal treatment for human autoimmune disease.

More than two decades ago, researchers discovered a type of T cell in humans that suppresses the immune system. Later, they found that, when defective, these so-called regulatory T cells are an underlying cause of autoimmune disease, specifically MS. For many years, however, the mechanism behind this dysfunction has remained unclear.

Autoimmune diseases, among the most common disorders of young adults, are known to be affected by genetic and environmental factors, including vitamin D deficiency and fatty acids. In an earlier study, researchers found that high levels of salt also contribute to the development of MS. Specifically, they observed that high salt induces inflammation in a type of immune cell known as CD4 T cells, while also causing a loss of regulatory T cell function. This, they found, is mediated by a salt-sensitive kinase, or an enzyme critical for cell signaling, known as SGK-1.

For this new study, Yale researchers used RNA sequencing to compare gene expression in patients with MS with expression in healthy individuals.  In patients with MS, the researchers identified upregulation, or increased expression, of a gene called PRDM1-S, a primate-specific variant of the protein BLIMP-1, which is involved in regulating immune function.

The researchers found that PRDM1-S induced increased expression of the salt-sensitive SGK-1 enzyme, leading to disruption of regulatory T cells. Moreover, they discovered similar overexpression of PRDM1-S in other autoimmune diseases, suggesting it may be a common feature of regulatory T cell dysfunction.

The researchers said that based on these insights, they are now developing drugs that can target and decrease expression of PRDM1-S in regulatory T cells. They have initiated collaborations with other Yale researchers using novel computational methods to increase the function of regulatory T cells to develop new approaches that will work across human autoimmune diseases.

The findings were published in the journal Science Translational Medicine.