| Literature DB >> 35107021 |
Aritra Bhattacharyya1,2, Kaveh Boostanpour1,2, Mohamed Bouzidi3,4, Liam Magee1,2, Tian Y Chen1,2, Rachel Wolters1,2, Paola Torre1,2, Satish K Pillai3,4, Mallar Bhattacharya1,2.
Abstract
Cx3cr1+ monocyte-derived macrophages (moMacs) are recruited to tissues after injury and are known to have profibrotic effects, but the cell-cell interactions and specific pathways that regulate this polarization and function are incompletely understood. Here we investigate the role of moMac-derived Pdgfa in bleomycin-induced lung fibrosis in mice. Deletion of Pdgfa with Cx3cr1-CreERT2 decreased bleomycin-induced lung fibrosis. Among a panel of in vitro macrophage polarizing stimuli, robust induction of Pdgfa was noted with IL10 in both mouse and human moMacs. Likewise, analysis of single-cell data revealed high expression of the receptor IL10RA in moMacs from human fibrotic lungs. Studies with IL10-GFP mice revealed that IL10-expressing cells were increased after injury in mice and colocalized with moMacs. Notably, deletion of IL10ra with Csf1r-Cre: IL10ra fl/fl mice decreased both Pdgfa expression in moMacs and lung fibrosis. Taken together, these findings reveal a novel, IL10-dependent mechanism of macrophage polarization leading to fibroblast activation after injury.Entities:
Keywords: IL10; Pdgfa; lung injury; macrophages; tissue fibrosis
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Year: 2022 PMID： 35107021 PMCID： PMC8917922 DOI： 10.1152/ajplung.00458.2021
Source DB: PubMed Journal: Am J Physiol Lung Cell Mol Physiol ISSN： 1040-0605 Impact factor: 6.011