Identification of IL-17F/frequent exacerbator endotype in asthma

Publication date: Available online 5 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Fabio L.M. Ricciardolo, Valentina Sorbello, Anna Folino, Fabio Gallo, Gian Mario Massaglia, Gabriella Favatà, Salvatore Conticello, Davide Vallese, Federica Gani, Mario Malerba, Gert Folkerts, Giovanni Rolla, Mirella Profita, Thais Mauad, Antonino Di Stefano, Giorgio Ciprandi
BackgroundSevere asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.ObjectiveTo study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics in relation to exacerbation rate.MethodsInflammatory cells and IL-17A⁺, IL-17F⁺, IL-21⁺, IL-22⁺ and IL-23⁺ cells were examined by immunohistochemistry (IHC) in cryostat sections of bronchial/nasal biopsies obtained from 33 SA (21 frequent exacerbators (FE)), 31 MA (3 FE) and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by IHC in bronchial tissue obtained from subjects died for fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F co-localization.ResultsHigher number (p<0.05) of neutrophils, IL-17A⁺, IL-17F⁺ and IL-21⁺ cells in bronchial biopsies and higher number (p<0.01) of IL-17F⁺ and IL-21⁺ cells in nasal biopsies were observed in SA compared to MA. Bronchial IL-17F⁺ cells correlated with bronchial neutrophils (r=0.54), exacerbation rate (r=0.41) and FEV1 (r=-0.46). Nasal IL-17F⁺ cells correlated with bronchial IL-17F (r=0.35), exacerbation rate (r=0.47) and FEV1 (r=-0.61). FE showed increased number of bronchial neutrophils/eosinophils/CD4⁺/CD8⁺ cells and bronchial/nasal IL-17F⁺ cells. ROC curve analysis evidenced predictive cut-off values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MA and SA and between FE and non-FE. IL-17F protein increased in bronchial/nasal lysates of SA and FE and in bronchial tissue of fatal asthma. IL-17F co-localized in CD4⁺/CD8⁺ cells.ConclusionsIL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation suggesting a pathogenic role of IL-17F in frequent exacerbators.

Teaser

Overexpression of nasal/bronchial IL-17F is a feature of severe asthma in relation to neutrophils, airway obstruction and exacerbation rate and it is also able to recognize frequent exacerbator phenotype potentially at risk of asthma death.


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