Macrophage-derived oncostatin M repairs the lung epithelial barrier during inflammatory damage
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. 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. Overall design: To examine the impact of the cytokine Oncostatin M (OSM) on alveolar epithelial phenotype, OSM-sufficient or -deficient mice were intra-tracheally treated with either saline (PBS) or recombinant OSM. RNA was subsequently isolated from FACS sorted  type II alveolar epithelial cells for analysis.