Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae
成果类型：
Article
署名作者：
Wei, Xiaoqin; Qian, Wei; Narasimhan, Harish; Chan, Ting; Liu, Xue; Arish, Mohd; Young, Samuel; Li, Chaofan; Cheon, In Su; Yu, Qing; Almeida-Santos, Gislane; Zhao, Xiao-Yu; Yeatts, Eric V.; Spear, Olivia J.; Yi, Megan; Parimon, Tanyalak; Fang, Yinshan; Hahn, Young S.; Bullock, Timothy N. J.; Somerville, Lindsay A.; Kaplan, Mark H.; Sperling, Anne I.; Shim, Yun Michael; Vassallo, Robert; Chen, Peter; Ewald, Sarah E.; Roden, Anja C.; Que, Jianwen; Jiang, Dianhua; Sun, Jie
署名单位：
University of Virginia; University of Virginia; University of Virginia; Cedars Sinai Medical Center; Cedars Sinai Medical Center; Columbia University; University of Virginia; University of Virginia; Indiana University System; Indiana University Indianapolis; Mayo Clinic; Mayo Clinic
刊物名称：
SCIENCE
ISSN/ISSBN：
0036-8491
DOI：
10.1126/science.adq2509
发表日期：
2025-03-07
关键词：
cell differentiation
pulmonary-fibrosis
host recovery
biogenesis
metabolism
expression
Covid-19
renewal
mouse
摘要：
Peroxisomes are vital but often overlooked metabolic organelles. We found that excessive interferon signaling remodeled macrophage peroxisomes. This loss of peroxisomes impaired inflammation resolution and lung repair during severe respiratory viral infections. Peroxisomes were found to modulate lipid metabolism and mitochondrial health in a macrophage type-specific manner and enhanced alveolar macrophage-mediated tissue repair and alveolar regeneration after viral infection. Peroxisomes also prevented excessive macrophage inflammasome activation and IL-1 beta release, limiting accumulation of KRT8(high) dysplastic epithelial progenitors following viral injury. Pharmacologically enhancing peroxisome biogenesis mitigated both acute symptoms and post-acute sequelae of COVID-19 (PASC) in animal models. Thus, macrophage peroxisome dysfunction contributes to chronic lung pathology and fibrosis after severe acute respiratory syndrome coronavirus 2 infection.