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Updated: Sep 16, 2025
Author Spotlight: Studying Macrophage-Epithelial Cell Interactions in Salivary Gland Regeneration After Injury
Published on: November 17, 2023
Macrophage-derived oncostatin M repairs the lung epithelial barrier during inflammatory damage
Daisy A Hoagland1,2, Patricia Rodríguez-Morales1,2, Alexander O Mann1,2
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
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.
Insights
Macrophage-derived oncostatin M (OSM) is crucial for lung repair after viral infection. OSM promotes epithelial cell growth, counteracting harmful type I interferon (IFN-I) responses and improving survival.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Restoring the lung epithelial barrier requires coordinated tissue repair and antiviral immunity.
- Type I interferons (IFN-I) are critical for antiviral defense but can impair tissue repair.
- The role of specific macrophage-derived factors in balancing these processes is not fully understood.
Purpose of the Study:
- To investigate the role of macrophage-derived oncostatin M (OSM) in lung epithelial repair following viral infection.
- To determine how OSM influences type I interferon (IFN-I) responses and epithelial cell homeostasis.
- To assess the therapeutic potential of OSM in mitigating infection-induced lung damage.
Main Methods:
- Utilized mouse models deficient in OSM.
- Administered influenza virus or viral mimics to induce infection and damage.
- Analyzed alveolar type II (ATII) epithelial cell states and proliferation.
- Assessed IFN-I responses, mortality, and morbidity.
- Evaluated OSM's effect on lung organoid formation in vitro.
Main Results:
- OSM-deficient mice showed altered ATII cell states at baseline.
- Lack of OSM led to heightened IFN-I responses and increased mortality after viral challenge.
- OSM administration induced ATII cell proliferation and protected deficient mice from morbidity.
- OSM promoted lung organoid formation, overcoming IFN-I-induced growth inhibition.
Conclusions:
- Oncostatin M (OSM) is an essential macrophage-derived growth factor for lung epithelial homeostasis.
- OSM counteracts the detrimental effects of type I interferon (IFN-I) during viral infections.
- OSM promotes epithelial cell proliferation, crucial for overcoming immunopathology and restoring lung function.
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