Cell Reports (Jun 2023)
Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease
- Theodore S. Kapellos,
- Kevin Baßler,
- Wataru Fujii,
- Christina Nalkurthi,
- Anna C. Schaar,
- Lorenzo Bonaguro,
- Tal Pecht,
- Izabela Galvao,
- Shobhit Agrawal,
- Adem Saglam,
- Erica Dudkin,
- Amit Frishberg,
- Elena de Domenico,
- Arik Horne,
- Chantal Donovan,
- Richard Y. Kim,
- David Gallego-Ortega,
- Tessa E. Gillett,
- Meshal Ansari,
- Jonas Schulte-Schrepping,
- Nina Offermann,
- Ignazio Antignano,
- Burcu Sivri,
- Wenying Lu,
- Mathew S. Eapen,
- Martina van Uelft,
- Collins Osei-Sarpong,
- Maarten van den Berge,
- Hylke C. Donker,
- Harry J.M. Groen,
- Sukhwinder S. Sohal,
- Johanna Klein,
- Tina Schreiber,
- Andreas Feißt,
- Ali Önder Yildirim,
- Herbert B. Schiller,
- Martijn C. Nawijn,
- Matthias Becker,
- Kristian Händler,
- Marc Beyer,
- Melania Capasso,
- Thomas Ulas,
- Jan Hasenauer,
- Carmen Pizarro,
- Fabian J. Theis,
- Philip M. Hansbro,
- Dirk Skowasch,
- Joachim L. Schultze
Affiliations
- Theodore S. Kapellos
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, 85764 Neuherberg, Germany
- Kevin Baßler
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Wataru Fujii
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Christina Nalkurthi
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW 2007, Australia
- Anna C. Schaar
- Institute of Computational Biology (ICB), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Department of Mathematics, Technische Universität München, 85748 Garching, Germany
- Lorenzo Bonaguro
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Platform for Single Cell Genomics and Epigenomics (PRECISE), German Center for Neurodegenerative Diseases and the University of Bonn, 53127 Bonn, Germany
- Tal Pecht
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Izabela Galvao
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW 2007, Australia
- Shobhit Agrawal
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Adem Saglam
- Platform for Single Cell Genomics and Epigenomics (PRECISE), German Center for Neurodegenerative Diseases and the University of Bonn, 53127 Bonn, Germany
- Erica Dudkin
- Computational Life Sciences, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Amit Frishberg
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Institute of Computational Biology (ICB), Helmholtz Zentrum München, 85764 Neuherberg, Germany
- Elena de Domenico
- Platform for Single Cell Genomics and Epigenomics (PRECISE), German Center for Neurodegenerative Diseases and the University of Bonn, 53127 Bonn, Germany
- Arik Horne
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Chantal Donovan
- University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW 2007, Australia; Immune Health, Hunter Medical Research Institute, New Lambton and The University of Newcastle, Newcastle, NSW 2305, Australia
- Richard Y. Kim
- University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW 2007, Australia; Immune Health, Hunter Medical Research Institute, New Lambton and The University of Newcastle, Newcastle, NSW 2305, Australia
- David Gallego-Ortega
- School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Garvan Institute of Medical Research, and St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Tessa E. Gillett
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9700 AB Groningen, the Netherlands; GRIAC Research Institute, University Medical Center Groningen, 9700 RB Groningen, the Netherlands
- Meshal Ansari
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Computational Biology (ICB), Helmholtz Zentrum München, 85764 Neuherberg, Germany
- Jonas Schulte-Schrepping
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Nina Offermann
- Immunregulation, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
- Ignazio Antignano
- Immunregulation, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
- Burcu Sivri
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Wenying Lu
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, 7250 TAS, Australia
- Mathew S. Eapen
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, 7250 TAS, Australia
- Martina van Uelft
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Collins Osei-Sarpong
- Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
- Maarten van den Berge
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9700 AB Groningen, the Netherlands; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
- Hylke C. Donker
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9700 AB Groningen, the Netherlands; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
- Harry J.M. Groen
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9700 AB Groningen, the Netherlands; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands
- Sukhwinder S. Sohal
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, 7250 TAS, Australia
- Johanna Klein
- Department of Internal Medicine II, Pneumology, University Hospital Bonn, 53127 Bonn, Germany
- Tina Schreiber
- Department of Internal Medicine II, Pneumology, University Hospital Bonn, 53127 Bonn, Germany
- Andreas Feißt
- University Clinics for Radiology, University Hospital Bonn, 53127 Bonn, Germany
- Ali Önder Yildirim
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, 85764 Neuherberg, Germany
- Herbert B. Schiller
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, 85764 Neuherberg, Germany
- Martijn C. Nawijn
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9700 AB Groningen, the Netherlands; GRIAC Research Institute, University Medical Center Groningen, 9700 RB Groningen, the Netherlands
- Matthias Becker
- Modular HPC and AI, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
- Kristian Händler
- Platform for Single Cell Genomics and Epigenomics (PRECISE), German Center for Neurodegenerative Diseases and the University of Bonn, 53127 Bonn, Germany; Institute of Human Genetics, University of Lübeck, 23562 Lübeck, Germany
- Marc Beyer
- Platform for Single Cell Genomics and Epigenomics (PRECISE), German Center for Neurodegenerative Diseases and the University of Bonn, 53127 Bonn, Germany; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
- Melania Capasso
- Immunregulation, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
- Thomas Ulas
- Platform for Single Cell Genomics and Epigenomics (PRECISE), German Center for Neurodegenerative Diseases and the University of Bonn, 53127 Bonn, Germany
- Jan Hasenauer
- Institute of Computational Biology (ICB), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Department of Mathematics, Technische Universität München, 85748 Garching, Germany; Computational Life Sciences, Life & Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany
- Carmen Pizarro
- Department of Internal Medicine II, Pneumology, University Hospital Bonn, 53127 Bonn, Germany
- Fabian J. Theis
- Institute of Computational Biology (ICB), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Department of Mathematics, Technische Universität München, 85748 Garching, Germany
- Philip M. Hansbro
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW 2007, Australia; University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW 2007, Australia
- Dirk Skowasch
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, 7250 TAS, Australia
- Joachim L. Schultze
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Department of Mathematics, Technische Universität München, 85748 Garching, Germany; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 6
p. 112525
Abstract
Summary: Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
