Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis
Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis
ABSTRACT Idiopathic pulmonary fibrosis (IPF) is the most severe form of lung fibrosis. It is progressive, and has an extremely poor outcome and limited treatment options. The disease exclusively affects the lungs, and thus less attention has been focused on blood-borne immune cells. which could be a more effective therapeutic target than lung-based cells. Here, we questioned if circulating monocytes, which has been shown to be increased in IPF, bore abnormalities that might contribute to its pathogenesis. We found that levels of circulating monocytes correlated directly with the extent of fibrosis in the lungs, and increased further during acute clinical deterioration. Monocytes in IPF were phenotypically distinct, displaying increased expression of CD64, a type 1 IFN gene expression signature and a greater magnitude of type 1 IFN response when stimulated. These abnormalities were accompanied by markedly raised CSF-1 levels in the serum, prolonged survival of monocytes ex vivo, and increased numbers of monocytes in lung tissue. Our study defines the key monocytic abnormalities in IPF, proposing type 1 IFN-primed monocytes as a potential driver of an aberrant repair response and fibrosis. It provides a rationale for targeting monocytes and identifies monocytic CD64 as a potential specific therapeutic target for IPF.
Rigby Rachel E、Fraser Emily、Blirando Karl、Zheng Yuejuan、Repapi Emmanouela、Taylor Stephen、Benamore Rachel、Hardman Clare S、Clelland Colin、Ho Ling-Pei、Vuppusetty Chaitanya、Hoyles Rachel、Rehwinkel Jan、Ashley Neil、Antanaviciute Agne、Alham Nasullah K、Iotchkova Valentina、Denney Laura、St Noble Victoria、Rastrick Joseph M D
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford||Department of Immunology and Microbiology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese MedicineDepartment of Computational Biology, Weatherall Institute of Molecular Medicine, University of OxfordDepartment of Computational Biology, Weatherall Institute of Molecular Medicine, University of OxfordDepartment of Thoracic Imaging, Oxford University Hospitals NHS Foundation TrustMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordDepartment of Thoracic Imaging, Oxford University Hospitals NHS Foundation TrustMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford||Oxford Interstitial Lung Disease Service, Oxford University Hospitals NHS Foundation TrustMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordDepartment of Thoracic Imaging, Oxford University Hospitals NHS Foundation TrustMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordSingle Cell Genomics Facility, Weatherall Institute of Molecular Medicine, University of OxfordMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordNuffield Department of Surgical Sciences and Oxford NIHR Biomedical Research Centre, University of Oxford, John Radcliffe HospitalDepartment of Computational Biology, Weatherall Institute of Molecular Medicine, University of OxfordMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of OxfordDepartment of Thoracic Imaging, Oxford University Hospitals NHS Foundation TrustImmunology Therapeutic Area
医药卫生理论基础医学内科学
Rigby Rachel E,Fraser Emily,Blirando Karl,Zheng Yuejuan,Repapi Emmanouela,Taylor Stephen,Benamore Rachel,Hardman Clare S,Clelland Colin,Ho Ling-Pei,Vuppusetty Chaitanya,Hoyles Rachel,Rehwinkel Jan,Ashley Neil,Antanaviciute Agne,Alham Nasullah K,Iotchkova Valentina,Denney Laura,St Noble Victoria,Rastrick Joseph M D.Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.01.16.908749.点此复制
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