Anti-inflammatory brain cells activated by signals from gut bacteria
New research published in the journal Nature is describing the discovery of a novel subset of brain cell with the capacity to prevent neuroinflammation. This anti-inflammatory activity is modulated by molecules induced by gut bacteria, revealing an exciting new gut-brain pathway that could guide research into a number of therapies for neurological disease.
The research, led by scientists from Brigham and Women’s Hospital, focused on astrocytes, a common type of non-neuronal cell abundant in the brain and spinal cord. Astrocytes play a number of diverse roles in the brain from helping regulate neural activity to maintaining the blood-brain barrier.
An increasing body of research over the past few years has uncovered the roles astrocytes play in promoting the inflammation that leads to neurodegeneration and neurological disease. This new study, however, suggests astrocytes can also protect the brain from inflammation.
“Over the years, many labs, including mine, have identified important roles for astrocytes in promoting neurological diseases,” explains Francisco Quintana, corresponding author on the new study. “This is the first case in which we’re showing that at least a subset of these cells (astrocytes) can prevent inflammation. The reason we haven’t seen this before was because we were studying these cells as if they were uniform, or one single cell type. But now we have the resolution to see the differences between these cells.”
Using a combination of RNA sequencing, high-throughput flow cytometry screening, and CRISPR gene perturbations the researchers identified a unique population of astrocytes found near the membrane that encloses the brain. These specific astrocytes express a pair of proteins that signal the destruction of rogue immune cells known to promote inflammation.
So what mechanism was triggering this anti-inflammatory astrocyte activity? It turns out bacteria in the gut modulate the expression of a signaling molecule called interferon-gamma. When this molecule reaches the brain it then induces these specific astrocytes to help kill the pro-inflammatory immune cells.
“Finding microbiome-controlled anti-inflammatory subsets of astrocytes is an important advance in our understanding of CNS inflammation and its regulation,” says Quintana. “This is a very novel mechanism by which the gut controls inflammation in the brain. It guides new therapies for neurological diseases, and we believe that this mechanism could contribute to the pathogenesis of brain tumors.”
Quintana also suggests there are most likely a number of other specific astrocyte populations yet to be discovered. And it seems increasingly likely that the activity of many of these unique astrocyte subsets could be controlled by gut-brain pathways.
“We have a list of other populations of astrocytes, and we’re working to see how the gut flora may control them.”
The new study was published in the journal Nature.
Source: Brigham and Women’s Hospital