Fabio L M Ricciardolo1, Valentina Sorbello2, Anna Folino2, Fabio Gallo3, Gian Mario Massaglia4, Gabriella Favatà5, Salvatore Conticello5, Davide Vallese6, Federica Gani4, Mario Malerba7, Gert Folkerts8, Giovanni Rolla9, Mirella Profita10, Thais Mauad11, Antonino Di Stefano6, Giorgio Ciprandi12. 1. Department of Clinical and Biological Sciences, Azienda Ospedaliera Universitaria (AOU) San Luigi Hospital, University of Torino, Torino, Italy. Electronic address: fabioluigimassimo.ricciardolo@unito.it. 2. Department of Clinical and Biological Sciences, Azienda Ospedaliera Universitaria (AOU) San Luigi Hospital, University of Torino, Torino, Italy. 3. Health Science Department, University of Genova, Genova, Italy. 4. Division of Respiratory Disease, AOU San Luigi Hospital, Torino, Italy. 5. Division of Ear, Nose, and Throat, AOU San Luigi Hospital, Torino, Italy. 6. Pulmonary Division, Fondazione S. Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Novara, Italy. 7. Department of Internal Medicine, University of Brescia, Brescia, Italy. 8. Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, The Netherlands. 9. Allergologia ed Immunologia Clinica, Ospedale Ordine Mauriziano "Umberto I," University of Torino, Torino, Italy. 10. Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy. 11. Department of Pathology, Sao Paulo University Medical School, São Paulo, Brazil. 12. IRCCS-AOU San Martino, Genova, Italy.
Abstract
BACKGROUND: Severe asthma might be associated with overexpression of Th17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways. OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate. METHODS: Inflammatory cells and IL-17A+, IL-17F+, IL-21+, IL-22+, and IL-23+ cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators [FEs]), 31 MAs (3 FEs), and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by immunohistochemistry in bronchial tissue obtained from subjects who died because of fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F colocalization. RESULTS: Higher number (P < .05) of neutrophils, IL-17A+, IL-17F+, and IL-21+ cells in bronchial biopsies and higher numbers (P < .01) of IL-17F+ and IL-21+ cells in nasal biopsies were observed in SAs compared with MAs. 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). FEs showed increased number of bronchial neutrophils/eosinophils/CD4+/CD8+ cells and bronchial/nasal IL-17F+ cells. Receiver operating characteristic curve analysis evidenced predictive cutoff values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MAs and SAs and between FEs and non-FEs. IL-17F protein increased in bronchial/nasal lysates of SAs and FEs and in bronchial tissue of fatal asthma. IL-17F colocalized in CD4+/CD8+ cells. CONCLUSIONS: IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs.
BACKGROUND: Severe asthma might be associated with overexpression of Th17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways. OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate. METHODS: Inflammatory cells and IL-17A+, IL-17F+, IL-21+, IL-22+, and IL-23+ cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators [FEs]), 31 MAs (3 FEs), and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by immunohistochemistry in bronchial tissue obtained from subjects who died because of fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F colocalization. RESULTS: Higher number (P < .05) of neutrophils, IL-17A+, IL-17F+, and IL-21+ cells in bronchial biopsies and higher numbers (P < .01) of IL-17F+ and IL-21+ cells in nasal biopsies were observed in SAs compared with MAs. 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). FEs showed increased number of bronchial neutrophils/eosinophils/CD4+/CD8+ cells and bronchial/nasal IL-17F+ cells. Receiver operating characteristic curve analysis evidenced predictive cutoff values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MAs and SAs and between FEs and non-FEs. IL-17F protein increased in bronchial/nasal lysates of SAs and FEs and in bronchial tissue of fatal asthma. IL-17F colocalized in CD4+/CD8+ cells. CONCLUSIONS:IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs.
Authors: Ankura Singh; Charles Liu; Barbara Putman; Rachel Zeig-Owens; Charles B Hall; Theresa Schwartz; Mayris P Webber; Hillel W Cohen; Kenneth I Berger; Anna Nolan; David J Prezant; Michael D Weiden Journal: Chest Date: 2018-07-17 Impact factor: 9.410
Authors: Karim H Shalaby; Miranda R Lyons-Cohen; Gregory S Whitehead; Seddon Y Thomas; Immo Prinz; Hideki Nakano; Donald N Cook Journal: J Allergy Clin Immunol Date: 2017-11-14 Impact factor: 10.793
Authors: Gabriele Pollara; Carolin T Turner; Joshua Rosenheim; Aneesh Chandran; Lucy C K Bell; Ayesha Khan; Amit Patel; Luis Felipe Peralta; Anna Folino; Ayse Akarca; Cristina Venturini; Tina Baker; Simone Ecker; Fabio L M Ricciardolo; Teresa Marafioti; Cesar Ugarte-Gil; David A J Moore; Benjamin M Chain; Gillian S Tomlinson; Mahdad Noursadeghi Journal: Sci Transl Med Date: 2021-05-05 Impact factor: 17.956