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Torn muscle? Send in the gut microbes for rapid repair

Torn muscle? Send in the gut microbes for rapid repair

The human immune system is incredibly versatile. Among its most skilled multitaskers are T cells, known for their role in everything from fighting infection to reining in inflammation to killing nascent tumors.

Now, in a surprising new discovery, Harvard Medical School researchers have found that a class of regulatory T cells (Tregs) made in the gut play a role in repairing injured muscles and mending damaged livers.

In an even more unexpected twist, the researchers found that gut microbes fuel the production of Tregs, which act as immune healers that go on patrol around the body and respond to distress signals from distant sites of injury.

The results, based on experiments in mice and published Feb. 22 in the journal Immunity, add to a growing body of evidence showing how important the gut microbiota is in regulating various physiologic functions beyond the gut. Additionally, the findings show that gut immune cells may have a far broader repertoire in taming inflammation and healing damage that extends beyond the intestines.

“Our observations indicate that gut microbes drive the production of a class of regulatory T cells that are constantly exiting the gut and act as sentries that sense damage at distant sites in the body and then act as emissaries to repair that damage,” said study senior author Diane Mathis, professor of immunology in the Blavatnik Institute at HMS.

The team cautions that the findings are based on experiments in mice and remain to be replicated in larger animals and in humans. However, the results raise interesting possibilities about harnessing the power of gut microbes to enhance recovery from injury.

Another tanatalizing possibility, Mathis said, is the potential to use this finding for designing therapies for fatty liver disease, a common condition in which accumulation of fat in the liver leads to liver cell damage and death.

A serendipitous clue

Regulatory T cells, or Tregs, are highly specialized. They reside in various organs, where they control local inflammation and regulate organ-specific immunity.

The researchers were already familiar with the type of Tregs normally found in the colon. These cells play an important role in maintaining gut health, such as protecting the body from food allergens, autoimmune conditions like colitis, and even colon cancer. Researchers also knew that gut microbes act as regulators of gut immunity by controlling the production of Tregs, but had seen scarce evidence that intestinal Tregs could affect tissues and processes beyond the gut.

So, when during a routine cataloging of various immune cells in different organs they came across gut Tregs intermingled with muscle cells, the researchers were baffled. These colonic Tregs had been rarely found outside of the small and large intestines.

“I stumbled upon some cells that looked very similar, and had all the same features of Tregs that derive from the gut,” said study first author Bola Hanna, a research fellow in immunology at HMS. “This caught our attention because we know these cells are produced in the gut and are shaped by the microbita.”

Why would muscle contain gut immune cells? The team decided to take a closer look.

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