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Alliance Researchers Discover a Subset of Brain Cells That Fight Inflammation with Instructions from Gut Bacteria

10/03/2021

 

Researchers of the International Progressive MS Alliance Collaborative Research Network led by Professor Francisco Quintana at Harvard’s Brigham and Women’s Hospital has reported that a subset of brain cells (astrocytes) may be directed by the body’s gut bacteria (microbiome) to tame brain inflammation, such as occurs in multiple sclerosis. Figuring out how to harness this beneficial activity may lead to new treatment approaches for MS, including probiotics to alter the balance of gut bacteria. 

 

 

  • Astrocytes are abundant in the brain and spinal cord, and in addition to providing beneficial support to other brain cells, they have also been shown capable of promoting inflammation and nerve degeneration.
  • This team now reports that a specific sub-population of astrocytes can turn off inflammation within the brain, based on signals regulated by the bacteria that reside in the gut.
  • They used advanced gene- and protein-analysis tools to identify the subset of astrocytes (notated as LAMP1+TRAIL+), which reside close to the membrane that encases the brain (meninges). Their qualities enable them to express proteins that can kill off inflammation-promoting immune T cells. Further work found that their proteins are regulated by an immune messenger (interferon gamma) that is instructed by gut bacteria.
  • Further research into understanding the mechanisms driving the potentially beneficial anti-inflammatory functions of these astrocytes could enable new therapeutic approaches to combat MS, such as customized probiotics to turn on this anti-inflammatory activity.
  • The team has also found that certain brain tumors use this same biological pathway to avoid destruction by the body’s immune responses, so this work may also lead to new therapies to prevent those tumors.
  • This research was funded by the International Progressive MS Alliance, the NIH and others. 

 

“This is a very novel mechanism by which the gut controls inflammation in the brain, said Dr. Quintana. “We have a list of other populations of astrocytes, and we’re working to see how the gut flora may control them.”
 
“Gut-licensed IFN-γ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes,” by Drs. Liliana M. Sanmarco, Michael A. Wheeler, Francisco Quintana (Brigham and Women’s Hospital and Broad Institute of MIT and Harvard), and international collaborators, was published on January 6, 2021 in Nature.
 

About the International Progressive MS Alliance

The Alliance exists to accelerate the development of effective treatments for people with progressive forms of multiple sclerosis to improve quality of life worldwide.  It is an unprecedented global collaboration of MS organisations, researchers, health professionals, the pharmaceutical industry, companies, trusts, foundations, donors and people affected by progressive MS, working together to address the unmet needs of people with progressive MS ─ rallying the global community to find solutions.  Our promise is more than hope, it is progress.

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