The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries

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...

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Veröffentlicht in:Immunity (Cambridge, Mass.) Mass.), 2023-04, Vol.56 (4), p.829-846.e8
Hauptverfasser: Hanna, Bola S., Wang, Gang, Galván-Peña, Silvia, Mann, Alexander O., Ramirez, Ricardo N., Muñoz-Rojas, Andrés R., Smith, Kathleen, Wan, Min, Benoist, Christophe, Mathis, Diane
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •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 Colonic RORγ+ Treg cells are a specialized microbiota-dependent population crucial for intestinal homeostasis, but their role in extra-gut tissues remains unexplored. Hanna et al. report that these cells seed non-mucosal tissues in response to injury wherein they can rein in IL-17A-driven inflammation, regulate stem cell activities, and promote tissue regeneration.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2023.01.033