New research into multiple sclerosis (MS) has revealed that the intestine provides a source of immune cells that reduces brain inflammation in MS patients. Furthermore, increasing the number of these cells blocked inflammation entirely in a preclinical model of the disease. The study was published today in Cell.
MS is an autoimmune disease that occurs when immune cells (including B and T cells) attack myelin. Recent studies have shown that drugs that target B cells mitigate MS, but those that target plasma cells make the disease worse. Why this might be had previously remained unclear.
The current study came about following the serendipitous meeting of two researchers—one from the University of Toronto and the other from the University of San Francisco—who both presented their findings at a conference and realized their labs’ findings aligned with each other.
Both teams had been looking into Immunoglobulin A (IgA) cells in MS. IgA cells originate as B cells in the bone marrow, but change their behavior when triggered by microbes in the gut.
The UCSF team had found evidence that inflammation-suppressing IgA was decreased in fecal samples from patients with active MS neuroinflammation, suggesting that they had been recruited to fight the disease. The U of T team had discovered complimentary findings in a mouse model. Both indicated that plasma cells that reside in the gut and produce IgA antibodies appear to migrate to the central nervous system and produce an anti-inflammatory effect during MS flare-ups.
Subsequent research in mice revealed that increasing the number of IgA plasma cells that migrate from the gut to the brain eradicated neuroinflammation, suggesting a therapeutic approach that employs these methods might be effective.
The next step for researchers will be to figure out what microbes in the gut promote generation of immunosuppressive IgA plasma cells. "If we can understand what these cells are reacting to, we can potentially treat MS by modulating our gut commensals," says Gommerman. "That might be easier than getting drugs into the brain, which is a strategy that hasn't always worked in MS."
Other questions might be to explore the role diet and other gut-mediating factors may have on MS disease progression.