TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages
Summary: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14...
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015717 |
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| author | Li Liu Pei Wu Yuqi Wei Meng Lu Haiyan Ge Ping Wang Jianlong Sun Tiffany Horng Xiucheng Liu Xiaoyong Shen Lingyun Sun Ying Xi |
| author_facet | Li Liu Pei Wu Yuqi Wei Meng Lu Haiyan Ge Ping Wang Jianlong Sun Tiffany Horng Xiucheng Liu Xiaoyong Shen Lingyun Sun Ying Xi |
| author_sort | Li Liu |
| collection | DOAJ |
| description | Summary: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14 (Fn14), the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is highly induced in myofibroblasts in the lungs of IPF patients and the bleomycin-induced lung fibrosis model. TWEAK-Fn14 signaling inhibits fibroblast activation and ECM synthesis and induces chemokine expression to recruit monocytes/macrophages into the lung. Fn14 deficiency increases ECM production and impairs macrophage infiltration and differentiation, leading to exacerbated lung fibrosis and impaired alveolar regeneration in a bleomycin model. Interestingly, Fn14 deficiency diminishes an injury-induced SiglecF− CD11b− MHCIIlo intermediate macrophage (IntermM) subpopulation, which promotes alveolar type II (AT2) cell proliferation in organoid cultures. These results collectively demonstrate a protective role of TWEAK-Fn14 signaling in lung fibrosis, highlighting the complexities and multilayered regulation of macrophage-fibroblast crosstalk. |
| format | Article |
| id | doaj-art-f5eddd3477a44e4c9d4f49bc7a9a1e2b |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-f5eddd3477a44e4c9d4f49bc7a9a1e2b2025-01-19T06:24:56ZengElsevierCell Reports2211-12472025-02-01442115220TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophagesLi Liu0Pei Wu1Yuqi Wei2Meng Lu3Haiyan Ge4Ping Wang5Jianlong Sun6Tiffany Horng7Xiucheng Liu8Xiaoyong Shen9Lingyun Sun10Ying Xi11School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, ChinaDepartment of Pulmonary and Critical Care Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Corresponding authorDepartment of Thoracic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Corresponding authorDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Corresponding authorSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China; Corresponding authorSummary: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14 (Fn14), the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is highly induced in myofibroblasts in the lungs of IPF patients and the bleomycin-induced lung fibrosis model. TWEAK-Fn14 signaling inhibits fibroblast activation and ECM synthesis and induces chemokine expression to recruit monocytes/macrophages into the lung. Fn14 deficiency increases ECM production and impairs macrophage infiltration and differentiation, leading to exacerbated lung fibrosis and impaired alveolar regeneration in a bleomycin model. Interestingly, Fn14 deficiency diminishes an injury-induced SiglecF− CD11b− MHCIIlo intermediate macrophage (IntermM) subpopulation, which promotes alveolar type II (AT2) cell proliferation in organoid cultures. These results collectively demonstrate a protective role of TWEAK-Fn14 signaling in lung fibrosis, highlighting the complexities and multilayered regulation of macrophage-fibroblast crosstalk.http://www.sciencedirect.com/science/article/pii/S2211124724015717CP: Immunology |
| spellingShingle | Li Liu Pei Wu Yuqi Wei Meng Lu Haiyan Ge Ping Wang Jianlong Sun Tiffany Horng Xiucheng Liu Xiaoyong Shen Lingyun Sun Ying Xi TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages Cell Reports CP: Immunology |
| title | TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages |
| title_full | TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages |
| title_fullStr | TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages |
| title_full_unstemmed | TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages |
| title_short | TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages |
| title_sort | tweak fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro regenerative macrophages |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015717 |
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