A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.
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Minutti CM
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK; Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: carlos.minutti@crick.ac.uk.
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Modak RV
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
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Macdonald F
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
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Li F
Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich, Zürich 8093, Switzerland.
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Smyth DJ
Wellcome Centre for Molecular Parasitology, Institute for Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
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Dorward DA
Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK; Division of Pathology, University of Edinburgh, Edinburgh EH4 2XU, UK.
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Blair N
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
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Husovsky C
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
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Muir A
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
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Giampazolias E
Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
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Dobie R
Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK.
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Maizels RM
Wellcome Centre for Molecular Parasitology, Institute for Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
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Kendall TJ
Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK; Division of Pathology, University of Edinburgh, Edinburgh EH4 2XU, UK.
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Griggs DW
Department of Molecular Microbiology and Immunology, Saint Louis University, Edward A. Doisy Research Center, St. Louis, MO 63104, USA.
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Kopf M
Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich, Zürich 8093, Switzerland.
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Henderson NC
Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK.
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Zaiss DM
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK. Electronic address: dietmar.zaiss@ed.ac.uk.
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English
The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-β) from latent complexes via integrin-αV activation. Using acute injury models in two different tissues, we found that by inducing TGF-β activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration after acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation.
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hybrid
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https://sonar.ch/global/documents/188307
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