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

doi:10.1016/j.celrep.2023.112525

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

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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 language	English
Article number	112525
Number of pages	30
Journal	Cell Reports
Volume	42
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2023.112525
State	Published - 27 Jun 2023
Externally published	Yes

Keywords

blood
bone marrow
chronic obstructive pulmonary disease
CP: Immunology
granulopoiesis
neutrophil
single-cell transcriptomics

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2023.112525

Cite this

Kapellos, T. S., Baßler, K., Fujii, W., Nalkurthi, C., Schaar, A. C., Bonaguro, L., Pecht, T., Galvao, I., Agrawal, S., Saglam, A., Dudkin, E., Frishberg, A., de Domenico, E., Horne, A., Donovan, C., Kim, R. Y., Gallego-Ortega, D., Gillett, T. E., Ansari, M., ... Schultze, J. L. (2023). Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease. Cell Reports, 42(6), Article 112525. https://doi.org/10.1016/j.celrep.2023.112525

@article{9c649a389db7431aa6b31bd825ff5adc,

title = "Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease",

abstract = "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.",

keywords = "blood, bone marrow, chronic obstructive pulmonary disease, CP: Immunology, granulopoiesis, neutrophil, single-cell transcriptomics",

author = "Kapellos, {Theodore S.} and Kevin Ba{\ss}ler and Wataru Fujii and Christina Nalkurthi and Schaar, {Anna C.} and Lorenzo Bonaguro and Tal Pecht and Izabela Galvao and Shobhit Agrawal and Adem Saglam and Erica Dudkin and Amit Frishberg and {de Domenico}, Elena and Arik Horne and Chantal Donovan and Kim, {Richard Y.} and David Gallego-Ortega and Gillett, {Tessa E.} and Meshal Ansari and Jonas Schulte-Schrepping and Nina Offermann and Ignazio Antignano and Burcu Sivri and Wenying Lu and Eapen, {Mathew S.} and {van Uelft}, Martina and Collins Osei-Sarpong and {van den Berge}, Maarten and Donker, {Hylke C.} and Groen, {Harry J.M.} and Sohal, {Sukhwinder S.} and Johanna Klein and Tina Schreiber and Andreas Fei{\ss}t and Yildirim, {Ali {\"O}nder} and Schiller, {Herbert B.} and Nawijn, {Martijn C.} and Matthias Becker and Kristian H{\"a}ndler and Marc Beyer and Melania Capasso and Thomas Ulas and Jan Hasenauer and Carmen Pizarro and Theis, {Fabian J.} and Hansbro, {Philip M.} and Dirk Skowasch and Schultze, {Joachim L.}",

note = "Funding Information: The authors would like to thank Anne O{\textquoteright}Garra for critical evaluation and feedback on the manuscript. W.F. was supported by a fellowship of the Alexander von Humboldt Foundation ( JPN-1186019-HFST-P ). J.L.S. received funds from the BMBF -funded excellence project Diet-Body-Brain (DietBB) under grant number 01EA1809A , the EU Horizon 2020 project SYSCID under grant 733100 , the EU Horizon 2020 Research and Innovation Program under grant agreement no. 874656 (discovAIR), the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation , projects numbers 347286815 , 329123747 , and 423957469 ), Germany{\textquoteright}s Excellence Strategy ( EXC2151-390873048 , ImmunoSensation 2 ), the Helmholtz-funded consortium Sparse2Big , and the Joint Programming Initiative , A Healthy Diet for a Healthy Life ( JPI HDHL ; project 529051018 ). M.C.N. acknowledges funding from the EU Horizon 2020 Research and Innovation Program under grant agreement no. 874656 (discovAIR). S.S.S. is funded by grants from Clifford Craig Foundation Launceston General Hospital . M.C. is funded by Helmholtz Zukunftsthema Immunology and Inflammation (ZT-0027). P.M.H. is funded by a fellowship and grants from the National Health and Medical Research Council (NHMRC) of Australia ( 1175134 ) and by UTS . Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jun,

day = "27",

doi = "10.1016/j.celrep.2023.112525",

language = "English",

volume = "42",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "6",

}

Kapellos, TS, Baßler, K, Fujii, W, Nalkurthi, C, Schaar, AC, Bonaguro, L, Pecht, T, Galvao, I, Agrawal, S, Saglam, A, Dudkin, E, Frishberg, A, de Domenico, E, Horne, A, Donovan, C, Kim, RY, Gallego-Ortega, D, Gillett, TE, Ansari, M, Schulte-Schrepping, J, Offermann, N, Antignano, I, Sivri, B, Lu, W, Eapen, MS, van Uelft, M, Osei-Sarpong, C, van den Berge, M, Donker, HC, Groen, HJM, Sohal, SS, Klein, J, Schreiber, T, Feißt, A, Yildirim, AÖ, Schiller, HB, Nawijn, MC, Becker, M, Händler, K, Beyer, M, Capasso, M, Ulas, T, Hasenauer, J, Pizarro, C, Theis, FJ, Hansbro, PM, Skowasch, D & Schultze, JL 2023, 'Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease', Cell Reports, vol. 42, no. 6, 112525. https://doi.org/10.1016/j.celrep.2023.112525

TY - JOUR

T1 - Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease

AU - Kapellos, Theodore S.

AU - Baßler, Kevin

AU - Fujii, Wataru

AU - Nalkurthi, Christina

AU - Schaar, Anna C.

AU - Bonaguro, Lorenzo

AU - Pecht, Tal

AU - Galvao, Izabela

AU - Agrawal, Shobhit

AU - Saglam, Adem

AU - Dudkin, Erica

AU - Frishberg, Amit

AU - de Domenico, Elena

AU - Horne, Arik

AU - Donovan, Chantal

AU - Kim, Richard Y.

AU - Gallego-Ortega, David

AU - Gillett, Tessa E.

AU - Ansari, Meshal

AU - Schulte-Schrepping, Jonas

AU - Offermann, Nina

AU - Antignano, Ignazio

AU - Sivri, Burcu

AU - Lu, Wenying

AU - Eapen, Mathew S.

AU - van Uelft, Martina

AU - Osei-Sarpong, Collins

AU - van den Berge, Maarten

AU - Donker, Hylke C.

AU - Groen, Harry J.M.

AU - Sohal, Sukhwinder S.

AU - Klein, Johanna

AU - Schreiber, Tina

AU - Feißt, Andreas

AU - Yildirim, Ali Önder

AU - Schiller, Herbert B.

AU - Nawijn, Martijn C.

AU - Becker, Matthias

AU - Händler, Kristian

AU - Beyer, Marc

AU - Capasso, Melania

AU - Ulas, Thomas

AU - Hasenauer, Jan

AU - Pizarro, Carmen

AU - Theis, Fabian J.

AU - Hansbro, Philip M.

AU - Skowasch, Dirk

AU - Schultze, Joachim L.

N1 - Funding Information: The authors would like to thank Anne O’Garra for critical evaluation and feedback on the manuscript. W.F. was supported by a fellowship of the Alexander von Humboldt Foundation ( JPN-1186019-HFST-P ). J.L.S. received funds from the BMBF -funded excellence project Diet-Body-Brain (DietBB) under grant number 01EA1809A , the EU Horizon 2020 project SYSCID under grant 733100 , the EU Horizon 2020 Research and Innovation Program under grant agreement no. 874656 (discovAIR), the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation , projects numbers 347286815 , 329123747 , and 423957469 ), Germany’s Excellence Strategy ( EXC2151-390873048 , ImmunoSensation 2 ), the Helmholtz-funded consortium Sparse2Big , and the Joint Programming Initiative , A Healthy Diet for a Healthy Life ( JPI HDHL ; project 529051018 ). M.C.N. acknowledges funding from the EU Horizon 2020 Research and Innovation Program under grant agreement no. 874656 (discovAIR). S.S.S. is funded by grants from Clifford Craig Foundation Launceston General Hospital . M.C. is funded by Helmholtz Zukunftsthema Immunology and Inflammation (ZT-0027). P.M.H. is funded by a fellowship and grants from the National Health and Medical Research Council (NHMRC) of Australia ( 1175134 ) and by UTS . Publisher Copyright: © 2023 The Authors

PY - 2023/6/27

Y1 - 2023/6/27

N2 - 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.

AB - 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.

KW - blood

KW - bone marrow

KW - chronic obstructive pulmonary disease

KW - CP: Immunology

KW - granulopoiesis

KW - neutrophil

KW - single-cell transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=85160438331&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2023.112525

DO - 10.1016/j.celrep.2023.112525

M3 - Article

C2 - 37243592

AN - SCOPUS:85160438331

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 6

M1 - 112525

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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