Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease

• Published in: Cell reports (Cambridge) Vol. 42; no. 6; p. 112525
• Main Authors: Kapellos, Theodore S., Baßler, Kevin, Fujii, Wataru, Nalkurthi, Christina, Schaar, Anna C., Bonaguro, Lorenzo, Pecht, Tal, Galvao, Izabela, Agrawal, Shobhit, Saglam, Adem, Dudkin, Erica, Frishberg, Amit, de Domenico, Elena, Horne, Arik, Donovan, Chantal, Kim, Richard Y., Gallego-Ortega, David, Gillett, Tessa E., Ansari, Meshal, Schulte-Schrepping, Jonas, Offermann, Nina, Antignano, Ignazio, Sivri, Burcu, Lu, Wenying, Eapen, Mathew S., van Uelft, Martina, Osei-Sarpong, Collins, van den Berge, Maarten, Donker, Hylke C., Groen, Harry J.M., Sohal, Sukhwinder S., Klein, Johanna, Schreiber, Tina, Feißt, Andreas, Yildirim, Ali Önder, Schiller, Herbert B., Nawijn, Martijn C., Becker, Matthias, Händler, Kristian, Beyer, Marc, Capasso, Melania, Ulas, Thomas, Hasenauer, Jan, Pizarro, Carmen, Theis, Fabian J., Hansbro, Philip M., Skowasch, Dirk, Schultze, Joachim L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27-06-2023; Cell Press; Elsevier
• Subjects: Animals; blood; bone marrow; chronic obstructive pulmonary disease; CP: Immunology; granulopoiesis; Humans; Inflammation; Lung; Mice; neutrophil; Neutrophils; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Emphysema; single-cell transcriptomics; CP: Immunology; single-cell transcriptomics; granulopoiesis; neutrophil; blood; bone marrow; chronic obstructive pulmonary disease
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112525

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.
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•Increase in blood neutrophil molecular states in early-stage COPD•Progenitor reprogramming is linked to altered blood neutrophil states•Neutrophil state abundance correlates with lung function decline
Kapellos et al. show that systemic molecular changes in neutrophils in early-stage COPD are associated with increased granulopoiesis and demonstrate that neutrophil transcriptomic states correlate with lung function decline.