1. Adenovirus-mediated Overexpression of FcγRIIB Attenuates Pulmonary Inflammation and Fibrosis.
- Author
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Zhe Zhang, Zhujie Cao, Lin Hou, Meiyue Song, Yitian Zhou, Yiling Chen, Huiyuan Hu, Yangfeng Hou, Ying Liu, Bolun Li, Xiaomin Song, Weipeng Ge, Baicun Li, Xuehan Jiang, Jie Yang, Dingyun Song, Xinri Zhang, Junling Pang, Tiantian Zhang, and Hong Zhang
- Subjects
PULMONARY fibrosis ,ADENOVIRUSES ,ALVEOLAR macrophages ,GENETIC overexpression ,GENETIC models ,INTERSTITIAL lung diseases - 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-g receptors (FcγRs) regulate macrophages and inflammation, but their roles in PF-ILDs remain unclear. We characterized the expression of FcγRs and found upregulated FcγRIIB in human and mouse lungs after 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 macrophagespecific overexpression of FcγRIIB and in mice treated with adenovirus by intratracheal instillation to upregulate 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 overexpression, representing a potential therapeutic strategy for PF-ILDs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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