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.
Free range bugz.
Obviously, the writer here is deficient, the sodium-potassium pump is the key metabilic mechanism of the body, translating this into “don’t salt your food” is igno.
I’m surprised this paper is being allowed to remain online! What an excellent find. Shameful how they have to throw in any mention of potential efficacy ... as a ‘cover’ to allow their paper to be published.
SO MUCH info in this paper. Thanks for posting and pinging.
FTS ...
ADVERSE EVENTS (AES)
Since billions of people have been vaccinated with one of the COVID-19 vaccines in a short time frame, it is easier to identify AEs linked to COVID-19 vaccination. Rare events of anaphylactic shock have been reported, above the average normal incidence in the population, after COVID-19 vaccination,5, 47, 129 in addition to various serious AEs. Although correlation does not necessarily mean causation, active monitoring and awareness of reported postvaccination AEs are essential. ...
...There is no point in being saved from COVID-19 through COVID-19 vaccination, but dying of a heart attack or crippled lifelong with a neurological disease due to an AE from the vaccines.
TREATMENT CONSIDERATIONS
Various antioxidants will be beneficial in the treatment of COVID-19 vaccine-induced AEs, by scavenging or chain-breaking ROS and peroxynitrite species, thereby converting them to less reactive products. Enzymatic antioxidants, such as superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase and glutathione transferase, as well as nonenzymatic endogenous molecules, such as N-acetylcysteine (NAC), taurine and GSH, could be used. Thiols and low molecular weight antioxidants, such as methylsulfonylmethane, tocopherols, ascorbate, retinol, urate and reduced GSH, would act as ‘the second line of defense’ against ROS.246
CONCLUSIONS
With substantial evidence indicating that the GVG Sp antigen, genetic material and LNPs used in COVID-19 vaccines can lead to endotheliopathy,13 a re-evaluation of DNA and mRNA vaccination is warranted. These components in the vaccines trigger the release of pro-inflammatory cytokines and excessive oxidative stress, negatively affecting the integrity of the GL through reduced sulfation and degradation. This impairment of GL function may result in skewed inflammatory responses, compromised immunity, oxidative stress, a procoagulatory state and various disease processes. In particular, COVID-19 vaccines did not prevent infection390, 391 or transmission,132, 392 and were associated with a significant risk of chronic disease, serious AEs or death.15, 20, 146, 179, 393, 394
That Yale researcher must have DEI credentials.
There’s danger in downgrading immune sensitivity. The immune system whole purpose is to kill and remove antigens which attack tissue, and to kill and remove tissue compromised by the attacks.
The key to solving autoimmune disease does not lie in eliminating or blunting immune response. It lies in eliminating or blunting the causative antigens.
Bkmk
Salt?
It’s hard to believe that a nutrient humans have been consuming since the dawn of time—one that is required for life—is the cause of so many human problems.
This is right up there with saying “water is bad for you.”
It’s clear researchers are just making stuff up in an attempt to get funding.
“And salt keeps forever.”
Because, salt is a metal.
Don’t forget coffee. Good, bad, good, bad.....
= = =
I cook my oatmeal in coffee.
Their alternating good, bad, cycles cancel each other out.
If you slice the apple and bake it, it's processed. Ditto the corn.
I'm down to drinking filtered water and consuming black tar heroin. And I'm just sure my doctor is going to say something about the water.
Well, did you lap it up from a lake? If it came out of a tap then it's processed. Let's not even go into the air we breathe.
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