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A spatially restricted fibrotic niche in pulmonary fibrosis is sustained by M-CSF/M-CSFR signalling in monocyte-derived alveolar macrophages

Joshi, Nikita ; Watanabe, Satoshi ; Verma, Rohan ; Jablonski, Renea P ; Chen, Ching-I ; Cheresh, Paul ; Markov, Nikolay S ; Reyfman, Paul A ; McQuattie-Pimentel, Alexandra C ; Sichizya, Lango ; Lu, Ziyan ; Piseaux-Aillon, Raul ; Kirchenbuechler, David ; Flozak, Annette S ; Gottardi, Cara J ; Cuda, Carla M ; Perlman, Harris ; Jain, Manu ; Kamp, David W ; Budinger, G R Scott ; Misharin, Alexander V

The European respiratory journal, 2020-01, Vol.55 (1), p.1900646 [Periódico revisado por pares]

England: European Respiratory Society

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Título:
A spatially restricted fibrotic niche in pulmonary fibrosis is sustained by M-CSF/M-CSFR signalling in monocyte-derived alveolar macrophages
Autor: Joshi, Nikita ; Watanabe, Satoshi ; Verma, Rohan ; Jablonski, Renea P ; Chen, Ching-I ; Cheresh, Paul ; Markov, Nikolay S ; Reyfman, Paul A ; McQuattie-Pimentel, Alexandra C ; Sichizya, Lango ; Lu, Ziyan ; Piseaux-Aillon, Raul ; Kirchenbuechler, David ; Flozak, Annette S ; Gottardi, Cara J ; Cuda, Carla M ; Perlman, Harris ; Jain, Manu ; Kamp, David W ; Budinger, G R Scott ; Misharin, Alexander V
Assuntos: Animals ; Fibrosis ; Humans ; Macrophage Colony-Stimulating Factor ; Macrophages - pathology ; Macrophages, Alveolar ; Mice ; Monocytes ; Original ; Pulmonary Fibrosis - chemically induced ; Pulmonary Fibrosis - pathology ; Receptor, Macrophage Colony-Stimulating Factor
É parte de: The European respiratory journal, 2020-01, Vol.55 (1), p.1900646
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms.We applied lineage tracing, single-cell RNA sequencing and single-molecule fluorescence hybridisation to a spatially restricted model of asbestos-induced pulmonary fibrosis.We demonstrate that tissue-resident alveolar macrophages, tissue-resident peribronchial and perivascular interstitial macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche. Deletion of monocyte-derived alveolar macrophages but not tissue-resident alveolar macrophages ameliorated asbestos-induced lung fibrosis. Monocyte-derived alveolar macrophages were specifically localised to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including platelet-derived growth factor subunit A. Using single-cell RNA sequencing and spatial transcriptomics in both humans and mice, we identified macrophage colony-stimulating factor receptor (M-CSFR) signalling as one of the novel druggable targets controlling self-maintenance and persistence of these pathogenic monocyte-derived alveolar macrophages. Pharmacological blockade of M-CSFR signalling led to the disappearance of monocyte-derived alveolar macrophages and ameliorated fibrosis.Our findings suggest that inhibition of M-CSFR signalling during fibrosis disrupts an essential fibrotic niche that includes monocyte-derived alveolar macrophages and fibroblasts during asbestos-induced fibrosis.
Editor: England: European Respiratory Society
Idioma: Inglês

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A spatially restricted fibrotic niche in pulmonary fibrosis is sustained by M-CSF/M-CSFR signalling in monocyte-derived alveolar macrophages

England: European Respiratory Society

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