A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation

Minutti CM, Modak R, Macdonald F, Li F, Smyth DJ, Dorward DA, Blair N, Husovsky C, Muir A, Giampazolias E, Dobie R, Maizels RM, Kendall TJ, Griggs DW, Kopf M, Henderson NC, Zaiss DM (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Immunity Elsevier

Book Volume: 50

Pages Range: 645-654.e6

Journal Issue: 3

DOI: 10.1016/j.immuni.2019.01.008

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-α V 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.

Involved external institutions

University of Edinburgh GB United Kingdom (GB) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH) University of Glasgow GB United Kingdom (GB) The Francis Crick Institute GB United Kingdom (GB) Saint Louis University (SLU) US United States (USA) (US)

How to cite

APA:

Minutti, C.M., Modak, R., Macdonald, F., Li, F., Smyth, D.J., Dorward, D.A.,... Zaiss, D.M. (2019). A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation. Immunity, 50(3), 645-654.e6. https://doi.org/10.1016/j.immuni.2019.01.008

MLA:

Minutti, Carlos M., et al. "A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation." Immunity 50.3 (2019): 645-654.e6.

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