Adenovirus-mediated Over-Expression of FcγRIIB Attenuates Pulmonary Inflammation and Fibrosis.
Am J Respir Cell Mol Biol
; 2022 Oct 13.
Article
in English
| MEDLINE | ID: covidwho-2237558
ABSTRACT
Progressive fibrosing interstitial lung diseases (PF-ILDs) result in high mortality and lack effective therapies. The pathogenesis of PF-ILDs involves macrophages driving inflammation and irreversible fibrosis. Fc-gamma receptors (FcγRs) regulate macrophages and inflammation, but their roles in PF-ILDs remain unclear. We characterized the expression of FcγRs and found up-regulated FcγRIIB in human and mouse lungs following exposure to silica. FcγRIIB deficiency aggravated lung dysfunction, inflammation and fibrosis in silica-exposed mice. Using single-cell transcriptomics and in vitro experiments, FcγRIIB was found in alveolar macrophages, where it regulated the expression of fibrosis-related genes Spp1 and Ctss. In mice with macrophage-specific over-expression of FcγRIIB, and in mice treated with adenovirus by intra-tracheal instillation to up-regulate FcγRIIB, silica-induced functional and histological changes were ameliorated. Our data from three genetic models and a therapeutic model suggest that FcγRIIB plays a protective role that can be enhanced by adenoviral over-expression, representing a potential therapeutic strategy for PF-ILDs.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Language:
English
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
Rcmb.2022-0056OC
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