Posted on 09/03/2024 5:25:40 AM PDT by Red Badger
Researchers at Yale have identified a protein that triggers loss of immune regulation associated with multiple sclerosis and other diseases.
This discovery, which highlights the role of environmental factors like high salt intake, offers a new target for developing universal autoimmune treatments.
Groundbreaking Discoveries in Autoimmune Research
More than two decades ago, a research team in the lab of David Hafler, a Yale researcher who at the time was at Harvard, discovered a type of T cell in humans that suppresses the immune system; they later found that these so-called regulatory T cells, when defective, are an underlying cause of autoimmune disease, specifically multiple sclerosis (MS). For many years, however, the mechanism behind this dysfunction has remained unclear.
In a new Yale-led study, a team of researchers finds 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.
The findings, published on August 28 in the journal Science Translational Medicine, also reveal a new target for a universal treatment for human autoimmune disease.
The research was led by Tomokazu Sumida, an assistant professor at Yale School of Medicine (YSM), and Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology at Yale.
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, 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, Sumida and Hafler found that high levels of salt also contribute to the development of multiple sclerosis, an autoimmune disease of the central nervous system. 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 enzyme critical for cell signaling, known as SGK-1.
For the new study, 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 (primate-specific transcription factor), also known as BLIMP-1, which is involved in regulating immune function.
New Potential Targets for Autoimmune Treatments
Surprisingly, PRDM1-S induced increased expression of the salt-sensitive SGK-1 enzyme, leading to disruption of regulatory T cells, the researchers found. Moreover, they found similar overexpression of PRDM1-S in other autoimmune diseases, suggesting that it may be a common feature of regulatory T cell dysfunction.
“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.”
Reference: “An autoimmune transcriptional circuit drives FOXP3+ regulatory T cell dysfunction” by Tomokazu S. Sumida, Matthew R. Lincoln, Liang He, Yongjin Park, Mineto Ota, Akiko Oguchi, Raku Son, Alice Yi, Helen A. Stillwell, Greta A. Leissa, Keishi Fujio, Yasuhiro Murakawa, Alexander M. Kulminski, Charles B. Epstein, Bradley E. Bernstein, Manolis Kellis and David A. Hafler, 28 August 2024, Science Translational Medicine. DOI: 10.1126/scitranslmed.adp1720
The study was done with Bradley Bernstein and Manolis Kellis, longtime collaborators of Hafler from the Broad Institute of MIT and Harvard, and several other research institutions.
Other authors from the Yale lab include neurologist Matthew R. Lincoln, and post-graduate research assistants Alice Yi, Helen Stillwell, and Greta Leissa.
Make up you mind!
This is a complete lie from the Devil. We need salt for life
all things in moderation.
Tune out the noise and you will live a much longer happier life.
Don’t forget coffee. Good, bad, good, bad.....
Despite the documented efficacy of this vaccination strategy................
Stopped reading right there...................
LOL!!!!
Now, THAT is funny
Gee, wasn’t a lot of salt used for hundreds of years to preserve food and all of a sudden it causes fatal diseases. In that case, why wasn’t the human race wiped out long ago?
We can still eat the bugs though, right?
Without salt.................
Just don’t put salt on the bugs.
Not only will I return to putting more salt on my food but I will add more butter and cook with lard!
Avoid high processed foods..heavy sugar..and high carbs. Get active (not to be confused with exercise)!
Yale? Right...
As long as za bugs they are not heavily processed.
“all things in moderation.”
You got it. Too much of anything can usually cause problems.
Isn’t that the university walz..the wanna be VP.. poo poos?
And just what do they consider *high salt levels?*?
And speaking of salt, a good, very valuable prepper item to add to your supplies.
Lack of salt in the diet can kill you. And yet salt is not available naturally in probably most places in the US.
But it now and store it in glass jars. I use used pasta sauce jars as the lids have a gasket built in that will help keep out moisture. And they seem far less prone to corrosion than canning jars and bands.
And salt keeps forever.
I always insist on free-range bugs, with no additives, preservatives or antibiotics.
IOW, eat REAL food.
Your body knows what to do with it and how to digest it.
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