IL10 trains macrophage profibrotic function after lung injury.
Aritra BhattacharyyaKaveh BoostanpourMohamed BouzidiLiam MageeTian Y ChenRachel WoltersPaola TorreSatish K PillaiMallar BhattacharyaPublished in: American journal of physiology. Lung cellular and molecular physiology (2022)
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.
Keyphrases
- single cell
- endothelial cells
- rna seq
- poor prognosis
- high fat diet induced
- stem cells
- type diabetes
- gene expression
- dendritic cells
- cell proliferation
- systemic lupus erythematosus
- cell death
- systemic sclerosis
- signaling pathway
- binding protein
- oxidative stress
- diabetic rats
- dna methylation
- high resolution
- metabolic syndrome
- idiopathic pulmonary fibrosis
- electronic health record
- skeletal muscle
- immune response
- interstitial lung disease
- mass spectrometry
- wild type
- pulmonary fibrosis
- cerebrospinal fluid
- pluripotent stem cells