DDX39B Considered ‘Guardian’ of Autoimmune Attacks, MS Risk | Protein Modulates Risk Factor Gene Activity, Regulatory T Cell Work

Emerging evidence suggests that the protein DDX39B is a master regulator of tolerance, the immune system’s ability to distinguish itself from potentially harmful non-self molecules, and helps control immune cell development key to this process. Studies have shown.

The findings suggest that activating DDX39B with small molecules may be a viable strategy for treating autoimmune diseases such as: multiple sclerosis (MS), the tolerance process is disrupted.

the study, “The RNA helicase DDX39B activates FOXP3 RNA splicing and controls T regulatory cell fate]was published. e-life.

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DDX39B alters the expression of genes that are potential MS risk factors

MS is caused by inflammation that damages the brain and spinal cord. It is not known exactly what causes this inflammation, but genetics is known to play an influencing role. disease risk.

The DDX39B protein (also known as UAP56) functions as a regulator of gene expression. Essentially, it helps turn other genes off or on. Previous studies have shown that DDX39B is important in regulating the expression of a gene called . IL7R, It is believed to be associated with the risk of MS.

This suggests that DDX39B itself may influence the risk of MS or other autoimmune diseases.

To find out, a team led by US scientists conducted a series of experiments in a cell model to see how the expression of hundreds of MS-associated genes changed when cells were engineered to lack the DDX39B protein. It was measured whether

Results showed that removal of DDX39B significantly altered the expression or activity of several (41 of 558) of these MS-associated genes. More specifically, DDX39B ablation increased the expression of genes associated with high MS risk and decreased the expression of genes associated with low MS risk.

“These data strongly suggest a shift in the gene expression signature from MS protective to MS pathogenicity upon DDX39B depletion, supporting a protective role of DDX39B in MS risk,” the researchers said. writing.

Further examination revealed that one of the genes regulated by DDX39B was FOXP3. This gene plays an important role in the development and activation of regulatory T cells (Treg).

Tregs are a type of immune cell important for maintaining immune tolerance, the ability of the immune system to recognize the body’s own healthy tissues and ensure that they are not being attacked. Autoimmune diseases like MS, by definition, are caused by the immune system mistakenly attacking healthy tissues, and are therefore essentially caused by a breakdown of normal immune tolerance. Strategies to activate T cells include: Being studied as a potential MS treatment.

‘Key guardians of immune tolerance’ may aid ‘true’ targeted therapies

Further experiments showed that the DDX39B protein FOXP3 Messenger RNA is an intermediate molecule that is made when a gene is “read” to make a protein. Scientists have identified how the DDX39B protein interacts at the molecular level. FOXP3 RNA.

Taken together, these data indicate that DDX39B is required for normal animal activity. FOXP3 gene. “Given the importance of FOXP3 in autoimmunity, this study establishes DDX39B as an important guardian of immune tolerance,” the researchers wrote.

“It’s worth noting that RNA-unwinding proteins are central to how we recognize our cells as our own without being confused with invading pathogens,” said the university study. Co-author Mariano Garcia Blanco, M.D., said:Said in an article in Virginia university press release.

These findings suggest that DDX39B activation may be a viable way to treat autoimmune diseases like MS, the researchers noted.

“For autoimmune diseases, we would like to activate DDX39B with small-molecule agonists. [activators]which has strong preclinical precedent,” said Chloe Nagasawa, a graduate student in Garcia Blanco’s lab and co-author of the study.

“We believe that a basic understanding of the molecular mechanisms that underpin immune tolerance will pave the way for truly targeted therapies,” Nagasawa added.