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

Authors
Kim, YM | Kim, H | Lee, S | Kim, S | Lee, JU | Choi, Y  | Park, HW | You, G | Kang, H | Lee, S | Park, JS | Park, Y | Park, HS  | Park, CS | Lee, SW
Citation
The European respiratory journal, 55(2). : 1900827-1900827, 2020
Journal Title
The European respiratory journal
ISSN
0903-19361399-3003
Abstract
Stratification of asthmatic patients based on relevant biomarkers enables the prediction of responsiveness against immune-targeted therapies in patients with asthma. Individualised therapy in patients with eosinophilic asthma has yielded improved clinical outcomes; similar approaches in patients with neutrophilic asthma have yet to be developed. We determined whether 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 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 bone marrow 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 interleukin (IL)-17A and tumour necrosis factor (TNF)-alpha; therefore, dual blockade of upstream stimuli using monoclonal antibodies or genetic deficiency of the cytokines in IL-17AxTNF-alpha double-knockout 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.
MeSH

DOI
10.1183/13993003.00827-2019
PMID
31744834
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Ajou Authors
박, 해심  |  최, 영우
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