Intestinal Neurons Help Inflammation in Our Immune System in Check
New research from Rockefeller University suggests that neurons play a role in protecting intestinal tissue from over-inflammation. The findings may help health experts develop better treatments for gastrointestinal diseases such as irritable bowel syndrome.
There are many types of immune cells present in the intestinal issue. Some of them are the Lamina propria macrophages which are found very close to the lining of the intestinal tube. Others are called muscularis macrophages are in a deeper tissue layer, more distant from what passes through the intestine.
In the study, researchers used an imaging study developed by Marc Tessier-Lavigne’s Laboratory of Brain Development and Repair. The technique allows scientists to view cellular structures three-dimensionally. Apart from the variations in how the cells look and move, they noticed that intestinal neurons are surrounded by macrophages.
Scientists analysed the genes that are expressed in the two macrophage populations. They found that lamina propria macrophages preferentially express pro-inflammatory genes. In contrast, the muscularis macrophages preferentially express anti-inflammatory genes, and these are boosted when intestinal infections occur.
"We wanted to know where this signal was coming from that induced this different response to infection," says assistant professor Daniel Mucida, head of the Laboratory of Mucosal Immunology. "We came to the conclusion that one of the main signals seems to come from neurons, which appear in our imaging to almost be hugged by the muscularis macrophages."
In other experiments, researchers found that muscularis macrophages carry receptors on their surface that allow them to respond to norepinephrine, a signalling substance produced by neurons. The presence of the receptor might indicate a mechanism by which neurons signal to the immune cells to put a stop to inflammation.
They also found that muscularis macrophages are activated within one to two hours following an infection—significantly faster than a response would take if it were completely immunological, not mediated by neurons. They believe that was because these deeply embedded macrophages receive signals from neurons, they are able to respond rapidly to an infection, even though they are not in direct contact with the pathogen.
"We now have a much better picture of how the communication between neurons and macrophages in the intestine helps to prevent potential damage from inflammation,"
"It’s plausible that a severe infection could disrupt this pathway, leading to the tissue damage and permanent gastrointestinal changes that are seen in diseases like irritable bowel syndrome. These findings could be harnessed in the future to develop treatments for such diseases."
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