Over twenty years ago Yale researchers discovered a type of T cell in humans that suppresses the immune system and later found that these so-called regulatory T cells, when defective, are an underlying cause of autoimmune disease, specifically multiple sclerosis (MS).
Loss of immune regulation
Now a new Yale study published in the journal Science Translational Medicine has found that this loss of immune regulation 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, and possibly reveals a new target for a universal treatment for human autoimmune disease.
“These experiments reveal a key underlying mechanism for the loss of immune regulation in MS and likely other autoimmune diseases,” said David Hafler, who is the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale and 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.”
Previous research
Autoimmune diseases are among the most common disorders of young adults, and they are known to be affected by genetic and environmental factors, such as vitamin D deficiency and fatty acids. In a previous study, Tomokazu Sumida, an assistant professor at Yale School of Medicine (YSM), and Hafler discovered that high levels of salt also contribute to the development of MS, which is an autoimmune disease of the central nervous system.
In this previous study, they specifically observed that high salt induces inflammation in CD4 T cells immune cells, while also causing a loss of regulatory T cell function. The researchers found that this was mediated by a salt-sensitive kinase, or enzyme critical for cell signaling, known as SGK-1.
Comparing gene expression
For the new study, RNA sequencing techniques were used to compare gene expression in MS patients with expression in healthy individuals. Among those with MS, the researchers identified the increased expression of the gene PRDM1-S (primate-specific transcription factor), also known as BLIMP-1, which is involved in regulating immune function.
Surprising findings
The researchers were surprised to find that PRDM1-S induced increased expression of the SGK-1 enzyme, leading to disruption of regulatory T cells. Additionally, a similar overexpression of PRDM1-S was found in other autoimmune diseases, suggesting that it may be a common feature of regulatory T-cell dysfunction.
Increasing regulatory T cell function
“Based on these insights, we are now developing drugs that can target and decrease expression of PRDM1-S in regulatory T cells,” Sumida said. “And we 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.”
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References/Sources/Materials provided by:
http://dx.doi.org/10.1126/scitranslmed.adp1720
https://news.yale.edu/2018/10/29/how-salt-can-trigger-inflammation-multiple-sclerosis
https://worldhealth.net/news/ginger-supplements-may-help-treat-autoimmune-diseases/
