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-SchreppingNina 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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number112525
Number of pages30
JournalCell reports
Issue number6
Early online date25-May-2023
Publication statusPublished - 27-Jun-2023

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