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

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.

journal_name

Immunity

journal_title

Immunity

authors

Minutti CM,Modak RV,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

doi

10.1016/j.immuni.2019.01.008

subject

Has Abstract

pub_date

2019-03-19 00:00:00

pages

645-654.e6

issue

3

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(19)30031-7

journal_volume

50

pub_type

杂志文章

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