“As a clinician-scientist, it is exciting that our experiments linking preclinical animal models to the biology we see in real MS patients may have uncovered a general mechanism for how the immune system counteracts inflammation,” said UCSF’s Pröbstel. “Until now, no one has really studied these IgA-producing plasma cells in the context of disease, but we are now examining them in detail in patients with MS to begin to understand how we might manipulate them to help treat neuroinflammatory disease.”
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 we can understand what these cells are reacting to, we can potentially treat MS by modulating our gut commensals,” said Gommerman, referring to the bacteria that live in the healthy gut. “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.
Gommerman plans to pursue the basic science behind these questions, working with Baranzini and other research groups to bring the findings into the clinical realm. “There is something very critical about how the gut and brain are connected, and we’re starting to unravel the molecular threads behind that clinical observation,” she said. “It’s a great example of how fast science can move.”
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