巨噬细胞来源的抑癌素M在炎症损伤期间修复肺上皮屏障

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-07-10 DOI:10.1126/science.adi8828

Daisy A. Hoagland, Patricia Rodríguez-Morales, Alexander O. Mann, Alan Y. Baez Vazquez, Shuang Yu, Alicia Lai, Harry Kane, Susanna M. Dang, Yunkang Lin, Louison Thorens, Shahinoor Begum, Martha A. Castro, Scott D. Pope, Jaechul Lim, Shun Li, Xian Zhang, Ming O. Li, Carla F. Kim, Ruaidhrí Jackson, Ruslan Medzhitov, Ruth A. Franklin

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引用次数: 0

摘要

组织修复程序必须与抗病毒免疫一起发挥作用，以恢复感染后的肺上皮屏障。我们发现巨噬细胞来源的抑癌素M （OSM）在小鼠感染和损伤期间抵消了I型干扰素（IFN-I）的病理作用。在基线时，osm缺陷小鼠表现出肺泡II型（ATII）上皮细胞状态的改变。在应对流感或病毒模拟挑战时，缺乏OSM的小鼠表现出更高的IFN-I反应和更高的死亡率。OSM给肺诱导ATII增殖，足以保护缺陷小鼠免于发病。此外，OSM促进了类器官的形成，尽管IFN-I有生长抑制作用。这些发现表明OSM是一种不可缺少的巨噬细胞来源的生长因子，它维持肺上皮细胞的稳态，促进其增殖以克服ifn - i介导的免疫病理。

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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. 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.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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