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

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Original languageEnglish
Number of pages16
JournalImmunity
Volume50
Early online date12 Feb 2019
DOIs
Publication statusPublished - 19 Mar 2019

Abstract

The Epidermal Growth Factor Receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis following injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functions by releasing bio-active TGFβ from latent complexes via integrin-αv activation. Using acute injury models in two different tissues, we found that by inducing TGFβ activation on mesenchymal stromal cells (aka pericytes), Amphiregulin induced their differentiation into myo-fibroblasts, 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 following 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.

    Research areas

  • Macrophages, TGFb, Amphiregulin, pericytes

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