Laboratory of Molecular Immunology, Department of Biological Applications and Technology, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Dimitrios Cassimos
Department of Pediatrics, University General Hospital of Alexandroupolis, Democritus University of Thrace Medical School, 68100 Thrace, Greece
Eugenia Roupakia
Laboratory of Biology, School of Medicine, Faculty of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Evangelos Kolettas
Laboratory of Biology, School of Medicine, Faculty of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Maria Panopoulou
Department of Microbiology, University General Hospital of Alexandroupolis, Democritus University of Thrace Medical School, 68100 Thrace, Greece
Elpis Mantadakis
Department of Pediatrics, University General Hospital of Alexandroupolis, Democritus University of Thrace Medical School, 68100 Thrace, Greece
Theocharis Konstantinidis
Laboratory of Molecular Immunology, Department of Biological Applications and Technology, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Akrivi Chrysanthopoulou
Laboratory of Molecular Immunology, Department of Biological Applications and Technology, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Childhood asthma is a chronic inflammatory airway disorder that can drive tissue remodeling. Neutrophils are amongst the most prominent inflammatory cells contributing to disease manifestations and may exert a potent role in the progression of inflammation to fibrosis. However, their role in asthma exacerbation is still understudied. Here, we investigate the association between neutrophil extracellular traps (NETs) and lung fibroblasts in childhood asthma pathophysiology using serum samples from pediatric patients during asthma exacerbation. Cell-based assays and NETs/human fetal lung fibroblast co-cultures were deployed. Increased levels of NETs and interleukin (IL)-17A were detected in the sera of children during asthma exacerbation. The in vitro stimulation of control neutrophils using the sera from pediatric patients during asthma exacerbation resulted in IL-17A-enriched NET formation. The subsequent co-incubation of lung fibroblasts with in vitro-generated IL-17A-enriched NETs led fibroblasts to acquire a pre-fibrotic phenotype, as assessed via enhanced CCN2 expression, migratory/healing capacity, and collagen release. These data uncover the important pathogenic role of the NET/IL-17A axis in asthma exacerbation, linking lung inflammation to fibroblast dysfunction and fibrosis.
