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Airway G-CSF identifies neutrophilic inflammation and contributes to asthma progression

Young-Min Kim, Hyekang Kim, Seungwon Lee, Sora Kim, Jong-Uk Lee, Youngwoo Choi, Han Wook Park, Gihoon You, Hansol Kang, Seyoung Lee, Jong-Sook Park, Yunji Park, Hae-Sim Park, Choon-Sik Park, Seung-Woo Lee
European Respiratory Journal 2019; DOI: 10.1183/13993003.00827-2019
Young-Min Kim
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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Hyekang Kim
2Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
6These authors contributed equally to this work
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Seungwon Lee
2Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
6These authors contributed equally to this work
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Sora Kim
2Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Jong-Uk Lee
3Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Gyeonggi-do, Republic of Korea
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  • ORCID record for Jong-Uk Lee
Youngwoo Choi
4Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
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Han Wook Park
2Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Gihoon You
2Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Hansol Kang
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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Seyoung Lee
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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Jong-Sook Park
5Division of Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Republic of Korea
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Yunji Park
2Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Hae-Sim Park
4Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
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Choon-Sik Park
5Division of Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Republic of Korea
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Seung-Woo Lee
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
2Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Abstract

Stratification of asthmatics based on relevant biomarkers enables it to predict the responsiveness against immune-targeted therapies in patients with asthma. Individualised therapy in patients with eosinophilic asthma has yielded improved clinical outcomes, and similar approaches in those with neutrophilic asthma have yet to be developed. We determined whether the colony stimulating factors (CSFs) in the airway reflect the inflammatory phenotypes of asthma and contribute to disease progression of neutrophilic asthma.

We analysed three different mouse models of asthma and assessed the cytokine profiles in sputum from human patients with asthma stratified according to inflammatory phenotype; in addition, we evaluated the therapeutic efficacy of various cytokine blockades in a mouse model of neutrophilic asthma.

Among the CSFs, airway granulocyte-CSF (G-CSF) contributes to airway neutrophilia by promoting neutrophil development in the bone marrow (BM), and thereby distinguishes neutrophilic inflammation from eosinophilic inflammation in mouse models of asthma. G-CSF is produced by concurrent stimulation of the lung epithelium with IL-17A and TNF-α; therefore, dual blockade of upstream stimuli using monoclonal antibodies or genetic deficiency of the cytokines in IL-17A × TNF-α double knockout (DKO) mice reduced the serum level of G-CSF, leading to alleviation of neutrophilic inflammation in the airway. In humans, the sputum level of G-CSF can be used to stratify patients with asthma with neutrophil-dominated inflammation.

Our results indicated that myelopoiesis-promoting G-CSF and cytokines as the upstream inducing factors are potential diagnostic and therapeutic targets in patients with neutrophilic asthma.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Kim reports In addition, Dr. Kim has a patent 10-2019-0057637 pending.

Conflict of interest: Dr. Kim has nothing to disclose.

Conflict of interest: Dr. Kim has nothing to disclose.

Conflict of interest: Dr. Kim reports In addition, Dr. Kim has a patent 10-2019-0057637 pending.

Conflict of interest: Dr. Lee has nothing to disclose.

Conflict of interest: Dr. Choi has nothing to disclose.

Conflict of interest: Dr. Park has nothing to disclose.

Conflict of interest: Dr. You has nothing to disclose.

Conflict of interest: Dr. Kang has nothing to disclose.

Conflict of interest: Dr. Lee has nothing to disclose.

Conflict of interest: Dr. Park has nothing to disclose.

Conflict of interest: Dr. Park has nothing to disclose.

Conflict of interest: Dr. Park has nothing to disclose.

Conflict of interest: Dr. Park reports In addition, Dr. Park has a patent 10-2019-0057637 pending.

Conflict of interest: Dr. Lee reports In addition, Dr. Lee has a patent 10-2019-0057637 pending.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received April 26, 2019.
  • Accepted November 5, 2019.
  • Copyright ©ERS 2019
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Airway G-CSF identifies neutrophilic inflammation and contributes to asthma progression
Young-Min Kim, Hyekang Kim, Seungwon Lee, Sora Kim, Jong-Uk Lee, Youngwoo Choi, Han Wook Park, Gihoon You, Hansol Kang, Seyoung Lee, Jong-Sook Park, Yunji Park, Hae-Sim Park, Choon-Sik Park, Seung-Woo Lee
European Respiratory Journal Jan 2019, 1900827; DOI: 10.1183/13993003.00827-2019

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Airway G-CSF identifies neutrophilic inflammation and contributes to asthma progression
Young-Min Kim, Hyekang Kim, Seungwon Lee, Sora Kim, Jong-Uk Lee, Youngwoo Choi, Han Wook Park, Gihoon You, Hansol Kang, Seyoung Lee, Jong-Sook Park, Yunji Park, Hae-Sim Park, Choon-Sik Park, Seung-Woo Lee
European Respiratory Journal Jan 2019, 1900827; DOI: 10.1183/13993003.00827-2019
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