The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries 2023 Hanna et al

Highlights

• Muscle injury induces local accumulation of RORγ+ Treg cells emanating from the gut
• The microbiota regulates muscle repair via RORγ+ Treg cells
• Muscle RORγ+ Treg cells shield differentiating muscle stem cells from IL-17A
• RORγ+ Treg cell emissaries play a general role in the homeostasis of extra-gut tissues

Summary
Specific microbial signals induce the differentiation of a distinct pool of RORγ+ regulatory T (Treg) cells crucial for intestinal homeostasis. We discovered highly analogous populations of microbiota-dependent Treg cells that promoted tissue regeneration at extra-gut sites, notably acutely injured skeletal muscle and fatty liver. Inflammatory meditators elicited by tissue damage combined with MHC-class-II-dependent T cell activation to drive the accumulation of gut-derived RORγ+ Treg cells in injured muscle, wherein they regulated the dynamics and tenor of early inflammation and helped balance the proliferation vs. differentiation of local stem cells. Reining in IL-17A-producing T cells was a major mechanism underlying the rheostatic functions of RORγ+ Treg cells in compromised tissues. Our findings highlight the importance of gut-trained Treg cell emissaries in controlling the response to sterile injury of non-mucosal tissues.

Paywall, https://www.cell.com/immunity/fulltext/S1074-7613(23)00045-6

 

"Without the trillions of bacteria in the gut, muscles might not be able to knit themselves back together after an injury. According to a study published February 22 in Immunity, T cells that normally reside in the mouse colon play a crucial role in tissue regeneration—and rely on gut microbes to do so. Without these helpful microbes, the study suggests, inflammation could get out of control, preventing healing and causing fibrosis.

“The main message of the paper is that the microbiota is influencing your immune system and your general health in a way larger way than we appreciated before,” says Bola Hanna, an immunologist at Harvard Medical School. Hanna studies regulatory T cells, a class of immune cells found in tissues throughout the body. He describes regulatory T cells as the “peacekeepers” of the immune system because they rein in other immune cells, ensuring inflammation doesn’t get out of control."

https://www.the-scientist.com/news-opinion/gut-bacteria-help-t-cells-heal-muscle-study-71007