Health
Molecular mechanisms of MS and other autoimmune diseases
More than 20 years ago, a team from the lab of Yale researcher David Hafler, then at Harvard, discovered a type of T cell that suppresses the human immune system. Defects in these so-called regulatory T cells were subsequently found to be an underlying cause of autoimmune diseases, notably multiple sclerosis (MS). However, the mechanism behind this dysfunction remained unknown for many years.
In a new Yale-led study, a team of researchers found that this loss of immune regulation is caused by an increase in PRDM1-S, a protein involved in immune function, and triggers a dynamic interplay of multiple genetic and environmental factors, including high salt intake.
The findings, published in the journal Science Translational Medicineand also revealed new targets for the universal treatment of human autoimmune diseases.
The study was led by Tomokazu Sumida, assistant professor at the Yale School of Medicine (YSM), and Hafler, the William S. and Lois Stiles Edgley Professor of Neurology and professor of immunobiology at Yale.
“These experiments reveal an important underlying mechanism of loss of immune regulation in MS and other autoimmune diseases,” said Hafler, who is also chair of Yale's Department of Neurology, “and also add mechanistic insight into how Tregs function.” [regulatory T cells] Dysfunction occurs in human autoimmune diseases.”
Autoimmune diseases are one of the most prevalent in young adults and are known to be influenced by genetic and environmental factors, such as vitamin D deficiency and fatty acids. In a previous study, Sumida and Hafler found that high salt concentrations also influence the development of multiple sclerosis, an autoimmune disease of the central nervous system. Specifically, they observed that high salt concentrations induce inflammation in a type of immune cell called CD4 T cells, while also causing a loss of regulatory T cell function. This phenomenon was found to be mediated by a salt-sensitive kinase or enzyme called SGK-1, which is essential for cell signaling.
In the new study, the researchers used RNA sequencing to compare gene expression in MS patients to that of healthy people. In MS patients, they 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, the researchers found that PRDM1-S causes increased expression of the salt-sensitive SGK-1 enzyme, leading to the destruction of regulatory T cells. Furthermore, similar PRDM1-S overexpression has been found in other autoimmune diseases, suggesting that this may be a general feature of regulatory T cell dysfunction.
“Based on these insights, we are now developing drugs that can target and reduce PRDM1-S expression in regulatory T cells,” Sumida said, “and with our new computational methods to enhance regulatory T cell function, we have begun to collaborate with other Yale researchers to develop a new approach that could have an impact across human autoimmune diseases.”
The research was conducted in collaboration with Hafler's longtime collaborators Bradley Bernstein and Manolis Kelis at the Broad Institute of MIT and Harvard University, as well as several other institutions.
Other authors from the Yale lab include neuroscientist Matthew R. Lincoln and graduate research assistants Alice Yi, Helen Stilwell and Greta Raisa.
|
Sources 2/ https://www.sciencedaily.com/releases/2024/08/240828224252.htm The mention sources can contact us to remove/changing this article |
What Are The Main Benefits Of Comparing Car Insurance Quotes Online
LOS ANGELES, CA / ACCESSWIRE / June 24, 2020, / Compare-autoinsurance.Org has launched a new blog post that presents the main benefits of comparing multiple car insurance quotes. For more info and free online quotes, please visit https://compare-autoinsurance.Org/the-advantages-of-comparing-prices-with-car-insurance-quotes-online/ The modern society has numerous technological advantages. One important advantage is the speed at which information is sent and received. With the help of the internet, the shopping habits of many persons have drastically changed. The car insurance industry hasn't remained untouched by these changes. On the internet, drivers can compare insurance prices and find out which sellers have the best offers. View photos The advantages of comparing online car insurance quotes are the following: Online quotes can be obtained from anywhere and at any time. Unlike physical insurance agencies, websites don't have a specific schedule and they are available at any time. Drivers that have busy working schedules, can compare quotes from anywhere and at any time, even at midnight. Multiple choices. Almost all insurance providers, no matter if they are well-known brands or just local insurers, have an online presence. Online quotes will allow policyholders the chance to discover multiple insurance companies and check their prices. Drivers are no longer required to get quotes from just a few known insurance companies. Also, local and regional insurers can provide lower insurance rates for the same services. Accurate insurance estimates. Online quotes can only be accurate if the customers provide accurate and real info about their car models and driving history. Lying about past driving incidents can make the price estimates to be lower, but when dealing with an insurance company lying to them is useless. Usually, insurance companies will do research about a potential customer before granting him coverage. Online quotes can be sorted easily. Although drivers are recommended to not choose a policy just based on its price, drivers can easily sort quotes by insurance price. Using brokerage websites will allow drivers to get quotes from multiple insurers, thus making the comparison faster and easier. For additional info, money-saving tips, and free car insurance quotes, visit https://compare-autoinsurance.Org/ Compare-autoinsurance.Org is an online provider of life, home, health, and auto insurance quotes. This website is unique because it does not simply stick to one kind of insurance provider, but brings the clients the best deals from many different online insurance carriers. In this way, clients have access to offers from multiple carriers all in one place: this website. On this site, customers have access to quotes for insurance plans from various agencies, such as local or nationwide agencies, brand names insurance companies, etc. "Online quotes can easily help drivers obtain better car insurance deals. All they have to do is to complete an online form with accurate and real info, then compare prices", said Russell Rabichev, Marketing Director of Internet Marketing Company. CONTACT: Company Name: Internet Marketing CompanyPerson for contact Name: Gurgu CPhone Number: (818) 359-3898Email: [email protected]: https://compare-autoinsurance.Org/ SOURCE: Compare-autoinsurance.Org View source version on accesswire.Com:https://www.Accesswire.Com/595055/What-Are-The-Main-Benefits-Of-Comparing-Car-Insurance-Quotes-Online View photos
to request, modification Contact us at Here or [email protected]
 |
 |
 |
