Estudio relaciona sistema inmune y su papel en la inflamación intestinal

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Estudio relaciona sistema inmune y su papel en la inflamación intestinal

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Study links gut neurons & immune system and their role in controlling inflammation

The immune system exercises consistent commitment to strengthen a physique from utmost threats—including what we eat and drink. As the digested food travels through the intestinal system a balancing act is played out. As a contingency measure, the immune cells must remain alert to act against damaging pathogens like Salmonella. However, their activity needs to be gradual else an overreaction can lead to equally harmful consequences like inflammation and tissue damage.


A group led by Daniel Mucida, head of the Laboratory of Mucosal Immunology at Rockefeller University found that neurons possibly protect intestinal tissue from over-inflammation. Their new findings were published in Cell on January 14. The group’s commentary on their research could have diagnostic implications for gastrointestinal diseases such as irritable bowel syndrome.

“Resistance to infections needs to be coupled with tolerance to the delicacy of the system,” says Mucida, who led the research together with co-first authors Ilana Gabanyi, a postdoctoral associate, and Paul Muller, a graduate student.

“Our work identifies a mechanism by which neurons work with immune cells to help intestinal tissue respond to perturbations without going too far.”

In order to view cellular structures in 3D, Mucida’s group made use of an imaging technique developed by Marc Tessier-Lavigne‘s Laboratory of Brain Development and Repair. This allowed the researchers to look at the differences between two different populations of macrophages in the intestine in excruciating detail.

Macrophages are large, specialized cells of the immune system that recognize, engulf and destroy target cells. Not only did they notice variations in how the cells look and move, they also noticed that intestinal neurons are surrounded by macrophages.

The team followed this up by analyzing the gene expression profile of these macrophage populations. The lamina propria macrophages (located close to intestinal lining) express genes responsible for inflammation. However, the muscularis macrophages (located in deeper tissue layers) 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 Mucida. “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.”

Furthermore, they observed that the muscularis macrophages are activated within 1-2 hours of an infection. This is much faster than an immunological response, suggesting an alternate signaling source. Upon carrying out more experiments, his group found that these macrophages carry receptors on their surface that allow them to respond to norepinephrine, a signaling 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.

“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,” says Mucida.

“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.”

Fuente: ... lammation/
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