Minutti, C. M. et al. (2019) A macrophage-pericyte axis directs tissue restoration via Amphiregulin-induced transforming growth factor beta activation. Immunity, 50(3), 645-654.e6. (doi: 10.1016/j.immuni.2019.01.008) (PMID:30770250) (PMCID:PMC6436929)
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Abstract
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.
| Item Type: | Articles |
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| Additional Information: | D.M.Z. has been supported by the Medical Research Council grant MR/M011755/1 and the European Union grant CIG-631413 (‘‘EGF-R for Immunity’’). N.C.H has been supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (103749) and T.J.K. by a Wellcome Trust Intermediate Clinical Fellowship (095898/Z/11/Z’). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Smyth, Dr Danielle and Maizels, Professor Rick |
| Authors: | Minutti, C. M., Modak, R. V., Macdonald, F., Li, F., Smyth, D. J., Dorward, D. A., Blair, N., Husovsky, C., Muir, A., Giampazolias, E., Dobie, R., Maizels, R. M., Kendall, T. J., Griggs, D. W., Kopf, M., Henderson, N. C., and Zaiss, D. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Immunity |
| Publisher: | Elsevier |
| ISSN: | 1074-7613 |
| ISSN (Online): | 1097-4180 |
| Published Online: | 12 February 2019 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Immunity 50(3): 645-654.e6 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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