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

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art_RICCIARDOLO_Identification_of_IL17Ffrequent_exacerbator_endotype_in_asthma_2017.PDF (3.65 MB)
Citações na Scopus
119
Tipo de produção
article
Data de publicação
2017
Editora
MOSBY-ELSEVIER
DOI
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Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
RICCIARDOLO, Fabio L. M.
SORBELLO, Valentina
FOLINO, Anna
GALLO, Fabio
MASSAGLIA, Gian Mario
FAVATA, Gabriella
CONTICELLO, Salvatore
VALLESE, Davide
GANI, Federica
MALERBA, Mario
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, v.140, n.2, p.395-406, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Severe asthma might be associated with overexpression of T(H)17 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 5 20.46). Nasal IL-17F(+) cells correlated with bronchial IL-17F (r = 0.35), exacerbation rate (r = 0.47), and FEV1 (r520.61). FEs showed increased number of bronchial neutrophils/eosinophils/CD4(+)/CD8(+) cells and bronchial/nasal IL-17F(1) 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.
Palavras-chave
Severe asthma, bronchial biopsy, nasal biopsy, IL-17F, neutrophils, frequent exacerbators, phenotype, endotype
URI
https://observatorio.fm.usp.br/handle/OPI/22012
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - ODS/03