Local administration of regulatory T cells promotes tissue healing.

Autor: Nayer B; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Tan JL; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Alshoubaki YK; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Lu YZ; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Legrand JMD; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Lau S; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Hu N; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Park AJ; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Wang XN; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Amann-Zalcenstein D; Advanced Genomics Facility, Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia., Hickey PF; Advanced Genomics Facility, Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia., Wilson T; MHTP Medical Genomics Facility, Monash Health Translation Precinct, Clayton, VIC, Australia., Kuhn GA; Institute for Biomechanics, ETH Zurich, Zurich, Switzerland., Müller R; Institute for Biomechanics, ETH Zurich, Zurich, Switzerland., Vasanthakumar A; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.; La Trobe University, Bundoora, VIC, Australia.; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia., Akira S; Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, Osaka, Japan., Martino MM; European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia. mikael.martino@monash.edu.; Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center, Osaka University, Osaka, Japan. mikael.martino@monash.edu.; Victorian Heart Institute, Monash University, Melbourne, VIC, Australia. mikael.martino@monash.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 09; Vol. 15 (1), pp. 7863. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1038/s41467-024-51353-2
Abstrakt: Regulatory T cells (Tregs) are crucial immune cells for tissue repair and regeneration. However, their potential as a cell-based regenerative therapy is not yet fully understood. Here, we show that local delivery of exogenous Tregs into injured mouse bone, muscle, and skin greatly enhances tissue healing. Mechanistically, exogenous Tregs rapidly adopt an injury-specific phenotype in response to the damaged tissue microenvironment, upregulating genes involved in immunomodulation and tissue healing. We demonstrate that exogenous Tregs exert their regenerative effect by directly and indirectly modulating monocytes/macrophages (Mo/MΦ) in injured tissues, promoting their switch to an anti-inflammatory and pro-healing state via factors such as interleukin (IL)-10. Validating the key role of IL-10 in exogenous Treg-mediated repair and regeneration, the pro-healing capacity of these cells is lost when Il10 is knocked out. Additionally, exogenous Tregs reduce neutrophil and cytotoxic T cell accumulation and IFN-γ production in damaged tissues, further dampening the pro-inflammatory Mo/MΦ phenotype. Highlighting the potential of this approach, we demonstrate that allogeneic and human Tregs also promote tissue healing. Together, this study establishes exogenous Tregs as a possible universal cell-based therapy for regenerative medicine and provides key mechanistic insights that could be harnessed to develop immune cell-based therapies to enhance tissue healing.
(© 2024. The Author(s).)
Databáze: MEDLINE
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