Gut neurons help immune system curb inflammation

New York: Neurons in the intestine send signals to immune cells to curb inflammation, according to a new study which may lead to new treatments for
gastrointestinal diseases such as irritable bowel syndrome.

The immune system exercises constant vigilance to protect the body from external threats - including what we eat and drink. A careful balancing act plays out as digested food travels through the intestine.

Immune cells must remain alert to protect against harmful pathogens like Salmonella, but their activity also needs to be tempered since an overreaction can lead to too much inflammation and permanent tissue damage.

Now, researchers from Rockefeller University in US have shown that neurons play a role in protecting intestinal tissue from over-inflammation. Different populations of macrophages are among the many types of immune cells present in intestinal tissue.

Lamina propria macrophages are found very close to the lining of the intestinal tube, while muscularis macrophages are in a deeper tissue layer, more distant from what passes through the intestine.

Using an imaging technique that allows scientists to view cellular structures three-dimensionally, researchers looked in depth at the differences between the two populations. In addition to variations in how the cells look and move, they noticed that intestinal neurons are surrounded by macrophages.

Researchers 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.

"Our work identifies a mechanism by which neurons work with immune cells to help intestinal tissue respond to perturbations without going too far," said Daniel Mucida from Rockefeller University.

"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," he added. Researchers observed that the 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.

"It is 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," said Mucida.

"These findings could be harnessed in the future to develop treatments for such diseases," he added. The findings were published in the journal Cell.