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

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)-α; therefore, dual blockade of upstream stimuli using monoclonal antibodies or genetic deficiency of the cytokines in IL-17A×TNF-α 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.
Competing Interests: Conflict of interest: Y-M. Kim has a patent 10-2019-0057637 pending. Conflict of interest: H. Kim has nothing to disclose. Conflict of interest: Seungwon Lee has nothing to disclose. Conflict of interest: S. Kim has a patent 10-2019-0057637 pending. Conflict of interest: J-U. Lee has nothing to disclose. Conflict of interest: Y. Choi has nothing to disclose. Conflict of interest: H.W. Park has nothing to disclose. Conflict of interest: G. You has nothing to disclose. Conflict of interest: H. Kang has nothing to disclose. Conflict of interest: Seyoung Lee has nothing to disclose. Conflict of interest: J-S. Park has nothing to disclose. Conflict of interest: Y. Park has nothing to disclose. Conflict of interest: H-S. Park has nothing to disclose. Conflict of interest: C-S. Park has a patent 10-2019-0057637 pending. Conflict of interest: S-W. Lee has a patent 10-2019-0057637 pending.
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