IL10 trains macrophage profibrotic function after lung injury.

Aritra Bhattacharyya, Kaveh Boostanpour, Mohamed Bouzidi, Liam Magee, Tian Y Chen, Rachel Wolters, Paola Torre, Satish K Pillai, Mallar Bhattacharya

American journal of physiology. Lung cellular and molecular physiology 2022 Mar 01

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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.

Citation

Aritra Bhattacharyya, Kaveh Boostanpour, Mohamed Bouzidi, Liam Magee, Tian Y Chen, Rachel Wolters, Paola Torre, Satish K Pillai, Mallar Bhattacharya. IL10 trains macrophage profibrotic function after lung injury. American journal of physiology. Lung cellular and molecular physiology. 2022 Mar 01;322(3):L495-L502