Glial cells essential for maintaining healthy intestinal immunity

Researchers at the Francis Crick Institute have discovered a fundamental role of glial cells in the nervous system of the intestine in maintaining a healthy gut. These cells have been found to coordinate the immune responses of the gut following an invasion of pathogens and could be key targets when exploring new treatments for inflammatory bowel conditions.

Maintaining a healthy gut and repairing tissue after infection or other types of injury is a complex process, and if it goes wrong it can lead to inflammatory bowel disease, such as Crohn’s disease and colitis. . While much previous research in this area has focused on the activity of different immune cells, many mysteries about the mechanisms behind these diseases remain unanswered, suggesting that other cells may play a vital role.

In their study, published in Nature today (October 20), researchers investigated the role of enteric glial cells in response to tissue damage. These cells are found in the intestinal wall and are part of the enteric nervous system that governs contractions of the intestinal muscles and other aspects of digestive function.

They infected mice with a common parasitic roundworm, Heligmosomoides polygyrus, and found that when the parasite invades the intestinal wall, a protein called gamma interferon is rapidly released by immune cells. Although this protein has so far been thought to target cells of the immune system, this new study has found that one of its primary targets is neighboring glial cells. The protein activates these cells which then release signals that attract other immune cells to the site of damage to fight infection.

To identify if similar mechanisms occur in humans, the researchers analyzed data previously collected by others from colon samples from people with ulcerative colitis, a long-term disease where the colon and rectum s ‘become inflamed and causes severe diarrhea and stomach cramps. As with mouse cells, genes associated with gamma interferon have also been activated in human glial cells. This suggests that the glial cells of the human intestine are also involved in the inflammatory conditions of this organ.

Fränze Progatzky, author and postdoctoral researcher at Crick’s Development and Homeostasis of the Nervous System Lab, says: “Unfortunately, currently treatments for inflammatory bowel disease are often limited to relieving symptoms rather than addressing the disease. cause. Our knowledge of the importance of enteric glial cells in maintaining a healthy gut opens the door to further studies of how these cells work and interact with the immune system and may in the future help us develop new potential treatments for these conditions.

The team also investigated the role of glial cells in maintaining healthy intestinal intestinal tissue in the absence of infection. They did this by blocking the ability of enteric glial cells to be activated by gamma interferon and found that this resulted in tissue inflammation even in normal mice. This shows that cells are also important outside of disease or injury in maintaining healthy intestinal tissue.

Vassilis Pachnis, author and group leader of the nervous system development and homeostasis laboratory at Crick, says: pathogens or toxins in other parts of the body. It will be exciting to explore this possibility further.

Reference: Progatzky F, Shapiro M, Chng SH et al. Regulation of intestinal immunity and tissue repair by enteric glia. Nature. 2021: 1-6. doi: 10.1038 / s41586-021-04006-z

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