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ResearchIn-Press PreviewInflammation Open Access | 10.1172/JCI173858
1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
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1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
Find articles by Halasz, L. in: JCI | PubMed | Google Scholar |
1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
Find articles by Oleksak, D. in: JCI | PubMed | Google Scholar
1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
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1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
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1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
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1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
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1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
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1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
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1Departments of Medicine and Biological Chemistry, Johns Hopkins University School of Medicine, St. Petersburg, United States of America
2Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
3Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany
4Myology Institute and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, United States of America
Find articles by Nagy, L. in: JCI | PubMed | Google Scholar |
Published August 27, 2024 - More info
Tissue regeneration is orchestrated by macrophages that clear damaged cells and promote regenerative inflammation. How macrophages spatially adapt and diversify their functions to support the architectural requirements of actively regenerating tissue remains unknown. In this study, we reconstructed the dynamic trajectories of myeloid cells isolated from acutely injured and early-stage dystrophic muscles. We identified divergent subsets of monocytes/macrophages and dendritic cells (DCs) and validated markers (e.g., GPNMB) and transcriptional regulators associated with defined functional states. In dystrophic muscle, specialized repair-associated subsets exhibited distinct macrophage diversity and reduced DC heterogeneity. Integrating spatial transcriptomics analyses with immunofluorescence uncovered the ordered distribution of subpopulations and multilayered regenerative inflammation zones (RIZs) where distinct macrophage subsets are organized in functional zones around damaged myofibers supporting all phases of regeneration. Importantly, intermittent glucocorticoid treatment disrupted the RIZs. Our findings suggest that macrophage subtypes mediated the development of the highly ordered architecture of regenerative tissues, unveiling the principles of the structured yet dynamic nature of regenerative inflammation supporting effective tissue repair.