Macrophage-derived oncostatin M repairs the lung epithelial barrier during inflammatory damage Journal Article
| Authors: | Hoagland, D. A.; Rodríguez-Morales, P.; Mann, A. O.; Baez Vazquez, A. Y.; Yu, S.; Lai, A.; Kane, H.; Dang, S. M.; Lin, Y.; Thorens, L.; Begum, S.; Castro, M. A.; Pope, S. D.; Lim, J.; Li, S.; Zhang, X.; Li, M. O.; Kim, C. F.; Jackson, R.; Medzhitov, R.; Franklin, R. A. |
| Article Title: | Macrophage-derived oncostatin M repairs the lung epithelial barrier during inflammatory damage |
| Abstract: | Tissue repair programs must function alongside antiviral immunity to restore the lung epithelial barrier following infection. We found that macrophage-derived oncostatin M (OSM) counteracted the pathological effects of type I interferon (IFN-I) during infection and damage in mice. At baseline, OSM-deficient mice exhibited altered alveolar type II (ATII) epithelial cell states. In response to influenza or viral mimic challenge, mice lacking OSM exhibited heightened IFN-I responses and increased mortality. OSM delivery to the lung induced ATII proliferation and was sufficient to protect deficient mice against morbidity. Furthermore, OSM promoted organoid formation despite the growth-inhibitory effects of IFN-I. These findings identify OSM as an indispensable macrophage-derived growth factor that maintains the homeostasis of lung epithelial cells and promotes their proliferation to overcome IFN-I–mediated immunopathology. Copyright © 2025 the authors, some rights reserved. |
| Keywords: | controlled study; genetics; mortality; interferon; nonhuman; flow cytometry; cell proliferation; animal cell; mouse; animal; metabolism; animals; mice; mice, knockout; animal tissue; gene expression; morbidity; animal experiment; animal model; inflammation; protein; genotype; pathology; enzyme linked immunosorbent assay; mice, inbred c57bl; physiology; c57bl mouse; immunology; neutrophil; gamma interferon; lung; epithelium cell; real time polymerase chain reaction; immunity; monocyte; macrophage; phagocytosis; macrophages; homeostasis; influenza; tissue injury; immunopathology; tissue repair; knockout mouse; repair; tumor necrosis factor; rna sequence; growth inhibition; orthomyxoviridae infections; interferon type i; lung alveolus cell type 2; cell component; female; article; oncostatin m; differential gene expression; lung alveolus epithelium cell; organoids; organoid; alveolar epithelial cells; osm protein, mouse; orthomyxovirus infection |
| Journal Title: | Science |
| Volume: | 389 |
| Issue: | 6756 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2025-07-10 |
| Start Page: | 169 |
| End Page: | 175 |
| Language: | English |
| DOI: | 10.1126/science.adi8828 |
| PUBMED: | 40638741 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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