The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries
- PMID: 36822206
- PMCID: PMC10101925
- DOI: 10.1016/j.immuni.2023.01.033
The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries
Abstract
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.
Keywords: IL-17; NASH; RORγ; Treg; colon; liver; microbiota; muscle; stem cell; tissue regeneration.
Copyright © 2023 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests D.M. is a co-founder and member of the Scientific Advisory Board of Abata Therapeutics.
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