The discovery could also be useful for other autoimmune diseases
University of Virginia neuroscientists have discovered a potential approach to disrupting the chronic inflammation responsible for multiple sclerosis. The new UVA study identifies a vital factor contributing to the overactive autoimmune response and neuroinflammation hallmarks of MS. The block of this building block in an MS research model has alleviated harmful inflammation, providing researchers with a prime target in their effort to develop new treatments for multiple sclerosis and other autoimmune diseases. The research was conducted by Andrea Merchake by her colleagues in the laboratory of Alban Gaultier, from the Department of Neuroscience at the University of Virginia School of Medicine and its Center for Brain Immunology and Glia (BIG).
“We are approaching the search for multiple sclerosis therapies from a new direction,” Merchak said. “By modulating the microbiome (the set of microorganisms that naturally live within us), we are making progress in understanding how the immune response can get out of control in autoimmunity. We can use this information to identify early interventions.”
Inflammation in multiple sclerosis
MS symptoms can include muscle spasms, stiffness, weakness, difficulty moving, depression, pain, and more. There is no cure, so treatments focus on helping patients manage symptoms, control flare-ups, and slow the progression of the disease. Scientists have struggled to understand the causes of MS, but recent research suggests an important role for gut microbiome. The new UVA findings strengthen this hypothesis, determining that an immune system regulator found in ‘barrier tissues’ such as the gut plays a vital role in the disease. According to the researchers, this regulator can reprogram the gut microbiome to promote chronic and harmful inflammation. Gaultier and his collaborators blocked the activity of the regulator, called “aryl hydrocarbon receptor,” in immune cells called T cells and found that this had a drastic effect on the production of bile acids and other metabolites in the microbiome of lab mice. With this receptor down, inflammation decreased and the mice recovered. The findings suggest that doctors may one day be able to take a similar approach to stopping harmful inflammation in people with MS, although this will require much more research. Before they can do that, scientists will need to better understand the interactions between the immune system and the microbiome, say the UVA researchers.
“Because of the complexity of the intestinal flora, probiotics are difficult to use clinically. This receptor can be easily targeted with drugs, so we may have found a more reliable route to promote a healthy gut microbiome,” Merchak said. “Ultimately, fine-tuning the immune response via the microbiome could save patients from the harsh side effects of immunosuppressive drugs.”
