한빛사논문
- 조회3,455
Young-Min Kim1, Hyekang Kim2,6, Seungwon Lee2,6, Sora Kim2, Jong-Uk Lee3, Youngwoo Choi4, Han Wook Park2, Gihoon You2, Hansol Kang1, Seyoung Lee1, Jong-Sook Park5, Yunji Park2, Hae-Sim Park4, Choon-Sik Park5 and Seung-Woo Lee1,2,*
1 Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
2 Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
3 Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Gyeonggi-do, Republic of Korea
4 Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
5 Division of Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Republic of Korea
6 These authors contributed equally to this work
*Correspondence : Seung-Woo Lee, Division of Integrative Biosciences & Biotechnology, Department of Life Sciences, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro. Nam-Gu. Pohang. Gyeongbuk. Korea 37673.
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.
논문정보
TOP52020년 후보
- Research article
- 2019년 11월 (BRIC 등록일 2019-12-09)
- 국내 연구진
- 생명과학 > 면역학
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