Blocking brain inflammation in multiple sclerosis with gut immune cells

While some immune cells cause the damaging brain inflammation of multiple sclerosis, others work to mitigate it. Researchers at the University of Toronto and the University of California, San Francisco, have discovered that some white blood cells produced in the gut can dampen brain inflammation in MS, a finding they believe could lead to a new therapeutic approach.

MS occurs when the body’s own immune system attacks the protective myelin coating around nerve cells. Past clinical studies have observed that targeting B cells can dampen inflammation but that reducing plasma cells—which develop from B cells—has the opposite effect. The scientists believe they’ve found an explanation for the different results.

The answer lies in gut plasma cells, which can be activated by gut microbes. In recent research published in Cell, the researchers studied mice and human MS samples and found that these cells produce IgA antibodies that travel to the central nervous system to produce an anti-inflammatory effect.

"Showing that IgA-producing B cells can travel from the gut to the brain opens a new page in the book of neuroinflammatory diseases and could be the first step towards producing novel treatments to modulate or stop MS and related neurological disorders," said study co-author Sergio Baranzini in a statement.

In stool samples from patients with active MS inflammation, the team found decreased level of IgA, suggesting the anti-inflammation cells had been recruited to fight the disease. And by increasing the number of those IgA-producing plasma cells, the researchers managed to stop brain inflammation in mice.

Over the past few years, researchers studying autoimmune disease have made progress in their efforts to understand what makes the immune system malfunction—and to come up with ways to counteract those autoimmune processes. A team at the Georgia Institute of Technology, for example, recently discovered a natural two-step process the body uses to recognize inflammation-prone T cells and push them toward destruction.  

The gut-brain axis has also attracted wide interest in CNS disorders. A recent study published in Nature by researchers at Harvard University Medical School showed that two proteins made by microglia play a key role in modulating inflammation in multiple sclerosis. Interestingly, molecules produced by gut bacteria are involved in producing the proteins.

The University of Toronto-UCSF researchers believe that growing the number of plasma cells that can migrate from the gut to the brain could hold promise as a new therapeutic for multiple sclerosis. And the team aims to find out which gut microbes promote the generation of these immunosuppressive cells.

"If we can understand what these cells are reacting to, we can potentially treat MS by modulating our gut commensals," said Jen Gommerman of the University of Toronto, the senior author of the study. "That might be easier than getting drugs into the brain, which is a strategy that hasn't always worked in MS."

Gommerman, Baranzini and colleagues plan to answer more questions about gut microbiome and MS, including whether certain lifestyles help those plasma cells to flourish, if a drug could build a nourishing environment for gut microbiome to produce these cells, and more.

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