In a new study, researchers have discovered that the intestine is the source of immune cells that reduce brain inflammation in people with multiple sclerosis (MS).
They also found that increasing the number of these cells blocks inflammation entirely in a preclinical model of the disease.
The research was conducted by researchers at the University of Toronto and UC San Francisco.
The cells in question are plasma cells—white blood cells that originate as B cells in the bone marrow but change their behavior when triggered by microbes in the gut.
The team studied mice and samples from human MS patients.
They found that plasma cells that reside in the gut and produce Immunoglobulin A (IgA) antibodies appear to migrate to the central nervous system and produce an anti-inflammatory effect during MS flare-ups.
MS is an autoimmune disease, driven by other types of immune cells (including B and T cells) that attack myelin, the protective coating that surrounds nerve fibers.
Recent clinical studies have shown drugs that target B cells mitigate MS, while those that target plasma cells make the disease worse.
The current study offers an explanation for these divergent results.
Canada and the U.S. have among the highest rates of MS in the world, with around three in every thousand individuals affected.
Symptoms can include fatigue, poor coordination, tingling, organ problems and cognitive impairment.
There is no cure, although quicker diagnoses and better drugs have improved outcomes significantly in the last 15 years.
Although IgAs comprise 80 per cent of all antibodies in the body, their exact function is still not fully understood.
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.
Specifically, the UCSF team found evidence that IgA was decreased in fecal samples from patients with active MS neuroinflammation.
This suggests that the inflammation-suppressing cells had been recruited to help fight the patients’ disease.
One promising aspect of the new research is that increasing the number of IgA plasma cells that migrate from the gut to the brain eradicated neuroinflammation in mice.
A therapeutic approach might aim to expand the number of these cells in the gut, enabling a plentiful supply that could move to the brain and dampen inflammation.
A key next step for the researchers is to figure out what microbes in the gut promote the generation of immunosuppressive IgA plasma cells.
If scientists can understand what these cells are reacting to, they can potentially treat MS by modulating our gut commensals.
That might be easier than getting drugs into the brain, which is a strategy that hasn’t always worked in MS.
The study also raises questions about the microbiome and lifestyle choices.
Do certain lifestyles nudge some people toward a gut microbiome that allows immunosuppressive plasma cells to flourish?
Are specific foods conducive to creating that environment and if so, might a drug or supplement mimic the effect?
Genetics are just one factor that affect susceptibility to MS; the current study highlights how non-genetic factors may confer disease resistance.
Jen Gommerman, Ph.D., a professor of immunology at the University of Toronto, is the senior author on the study.
The results are published in Cell.
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Source: Cell.
