Summary: According to research, higher levels of the protein PRDM1-S, which are caused by high salt intake, interfere with immune regulation and contribute to multiple sclerosis ( MS ) autoimmune diseases.
This finding reveals how economic factors, such as diet, does affect biological systems, leading to T cell function. The research suggests that the use of PRDM1-S as a therapeutic agent for a variety of immune conditions.
Important Information:
- Increased PRDM1-S appearance affects defensive rules, contributing to MS and other inflammatory conditions.
- High sodium consumption induces overexpression of PRDM1-S, leading to regulation T cell function.
- As a possible widespread treatment for inflammatory diseases, researchers are developing drugs to lower PRDM1-S manifestation.
Origin: Yale
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, yet, the process behind this function has remained unclear.
A team of researchers at Yale University discovered that this loss of immune legislation is caused by a rise in PRDM1-S, a protein essential for immune function, which triggers a powerful connection between a number of genetic and environmental factors, including higher water uptake.
The findings,  , published in the journal , Science Translational Medicine, even reveal a new destination for a common treatment for people allergic disease.
The research was led by , Tomokazu Sumida, a professor of immunobiology at Yale School of Medicine ( YSM), and Hafler, a professor of neurology and immunobiology at Yale.
According to Hafler, who is also the head of Yale’s Department of Neurology,” These experiments reveal a crucial underlying mechanism for the loss of immune regulation in MS and likely other immune conditions.”
They furthermore add molecular insight into how Treg]regulatory T cells ] difficulties occurs in people immune illnesses.”
Parmi the most prevalent problems of young people, inflammatory diseases, are known to be caused by genetic and environmental factors, including vitamin D inadequacy and fatty acids.
In a prior research, Sumida and Hafler discovered that higher levels of sodium also contribute to the development of multiple sclerosis, a central nervous system immune disorder. Especially, they observed that high sugar induces disease in a type of immune body known as CD4 T cells, while even causing a decline 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.
Researchers used RNA sequencing to compare the expression levels of MS patients and healthy individuals for the new study. 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.
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 begun working with other Yale researchers to improve the function of regulatory T cells by using novel computational techniques to improve the ability of them to respond to new treatments for autoimmune diseases in humans.
Bradley Bernstein and Manolis Kellis, former Hafler collaborators at the Harvard and MIT Broad Institute, as well as a number of other research institutions, co-authors of the study.
Other authors from the Yale lab include neurologist Matthew R. Lincoln, and post-graduate research assistants Alice Yi, Helen Stillwell, and Greta Leissa.
About this news from multiple sclerosis research
Author: Bess Connolly
Source: Yale
Contact: Bess Connolly – Yale
Image: The image is credited to Neuroscience News
Original Research: Closed access.
By David Hafler et al.,” A transcriptional autoimmune circuit causes FOXP3+ , regulatory T cell dysfunction.” Science Translational Medicine
Abstract
An autoimmune transcriptional circuit drives FOXP3+ , regulatory T cell dysfunction
Autoimmune diseases, among the most common disorders of young adults, are mediated by genetic and environmental factors. Although CD4+FOXP3+ , regulatory T cells ( Tregs ) play a central role in preventing autoimmunity, the molecular mechanism underlying their dysfunction is unknown.
In the autoimmune disease multiple sclerosis ( MS ), we performed comprehensive transcriptomic and epigenomic profiling of Tregs  to identify crucial transcriptional programs regulating human autoimmunity.
We found that up-regulation of a primate-specific short isoform of PR domain zinc finger protein 1 ( PRDM1-S) induces expression of serum and glucocorticoid-regulated kinase 1 (SGK1 ) independent from the evolutionarily conserved long , PRDM1, which led to destabilization of forkhead box P3 ( FOXP3 ) and Treg , dysfunction. This aberrant , PRDM1-S/SGK1 , axis is shared among other autoimmune diseases.
Furthermore, the chromatin landscape profiling in Tregs , from individuals with MS revealed enriched activating protein–1 ( AP-1 ) /interferon regulatory factor ( IRF ) transcription factor binding as candidate upstream regulators of , PRDM1-S , expression and Treg , dysfunction.
Our study uncovers a mechanistic model where the evolutionary emergence of , PRDM1-S , and epigenetic priming of AP-1/IRF may be key drivers of dysfunctional Tregs , in autoimmune diseases.
