Macrophage-derived oncostatin M repairs the lung epithelial barrier during inflammatory damage

• 成果类型: Article
• 署名作者: Hoagland, Daisy A.; Rodriguez-Morales, Patricia; Mann, Alexander O.; Baez Vazquez, Alan Y.; Yu, Shuang; Lai, Alicia; Kane, Harry; Dang, Susanna M.; Lin, Yunkang; Thorens, Louison; Begum, Shahinoor; Castro, Martha A.; Pope, Scott D.; Lim, Jaechul; Li, Shun; Zhang, Xian; Li, Ming O.; Kim, Carla F.; Jackson, Ruaidhri; Medzhitov, Ruslan; Franklin, Ruth A.
• 署名单位: Harvard University; Harvard University; Harvard Medical School; Yale University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Northeastern University; Memorial Sloan Kettering Cancer Center; Harvard University; Howard Hughes Medical Institute; Yale University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8876
• DOI: 10.1126/science.adi8828
• 发表日期: 2025-07-10
• 页码: 169-175
• 关键词: 1st line; biology; DEFENSE; HEALTH; cells

摘要

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.