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

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

doi:10.1016/j.jaci.2016.10.034

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

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

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Severe asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.

OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics 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 (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.

RESULTS: Higher 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.

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 frequent exacerbators.

Original language	English
Journal	Journal of Allergy and Clinical Immunology
DOIs	https://doi.org/10.1016/j.jaci.2016.10.034
Publication status	Published - Aug 2017

Keywords

severe asthma
bronchial biopsy
nasal biopsy
IL-17F
neutrophils
frequent exacerbators
phenotype
endotype

Access to Document

10.1016/j.jaci.2016.10.034

1-s2.0-S0091674916314427-mainFinal published version, 3.65 MBLicence: Taverne

Cite this

Ricciardolo, F. L. M., Sorbello, V., Folino, A., Gallo, F., Massaglia, G. M., Favatà, G., Conticello, S., Vallese, D., Gani, F., Malerba, M., Folkerts, G., Rolla, G., Profita, M., Mauad, T., Di Stefano, A., & Ciprandi, G. (2017). Identification of IL-17F/frequent exacerbator endotype in asthma. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.10.034

@article{18e0017f4ad648b8bf0579dfa8522b39,

title = "Identification of IL-17F/frequent exacerbator endotype in asthma",

abstract = "BACKGROUND: Severe asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics 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 (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.RESULTS: Higher 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.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 frequent exacerbators.",

keywords = "severe asthma, bronchial biopsy, nasal biopsy, IL-17F, neutrophils, frequent exacerbators, phenotype, endotype",

author = "Ricciardolo, \{Fabio L M\} and Valentina Sorbello and Anna Folino and Fabio Gallo and Massaglia, \{Gian Mario\} and Gabriella Favat{\`a} and Salvatore Conticello and Davide Vallese and Federica Gani and Mario Malerba and Gert Folkerts and Giovanni Rolla and Mirella Profita and Thais Mauad and \{Di Stefano\}, Antonino and Giorgio Ciprandi",

note = "Copyright {\^A}{\textcopyright} 2016. Published by Elsevier Inc.",

year = "2017",

month = aug,

doi = "10.1016/j.jaci.2016.10.034",

language = "English",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Identification of IL-17F/frequent exacerbator endotype in asthma

AU - Ricciardolo, Fabio L M

AU - Sorbello, Valentina

AU - Folino, Anna

AU - Gallo, Fabio

AU - Massaglia, Gian Mario

AU - Favatà, Gabriella

AU - Conticello, Salvatore

AU - Vallese, Davide

AU - Gani, Federica

AU - Malerba, Mario

AU - Folkerts, Gert

AU - Rolla, Giovanni

AU - Profita, Mirella

AU - Mauad, Thais

AU - Di Stefano, Antonino

AU - Ciprandi, Giorgio

PY - 2017/8

Y1 - 2017/8

N2 - BACKGROUND: Severe asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics 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 (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.RESULTS: Higher 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.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 frequent exacerbators.

AB - BACKGROUND: Severe asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics 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 (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.RESULTS: Higher 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.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 frequent exacerbators.

KW - severe asthma

KW - bronchial biopsy

KW - nasal biopsy

KW - IL-17F

KW - neutrophils

KW - frequent exacerbators

KW - phenotype

KW - endotype

U2 - 10.1016/j.jaci.2016.10.034

DO - 10.1016/j.jaci.2016.10.034

M3 - Article

C2 - 27931975

SN - 0091-6749

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this