TY - JOUR
T1 - Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17(+) Cells in Asthmatic Airways
AU - Fattahi, Fatemeh
AU - Brandsma, Corry-Anke
AU - Lodewijk, Monique
AU - Reinders-Luinge, Marjan
AU - Postma, Dirkje S.
AU - Timens, Wim
AU - Hylkema, Machteld N.
AU - Hacken, ten, Nicolaas
PY - 2016/8/23
Y1 - 2016/8/23
N2 - BackgroundInterleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source.MethodsBronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17.ResultsIn non-ICS users, nonatopic asthmatics had more IL-17(+) cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17(+) cells, independent of smoking. The number of IL-17(+) cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17-0.35) and eosinophils (B: 0.18, 95% CI: 0.07-0.29). The majority of IL-17(+) cells were neutrophils, as confirmed by double immunostaining.ConclusionsWe show for the first time that atopy and ICS use are associated with lower numbers of IL-17(+) cells in asthmatic airways. Importantly, IL-17(+) cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17.
AB - BackgroundInterleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source.MethodsBronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17.ResultsIn non-ICS users, nonatopic asthmatics had more IL-17(+) cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17(+) cells, independent of smoking. The number of IL-17(+) cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17-0.35) and eosinophils (B: 0.18, 95% CI: 0.07-0.29). The majority of IL-17(+) cells were neutrophils, as confirmed by double immunostaining.ConclusionsWe show for the first time that atopy and ICS use are associated with lower numbers of IL-17(+) cells in asthmatic airways. Importantly, IL-17(+) cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17.
KW - T(H)17 CELLS
KW - TH17 CELLS
KW - INFLAMMATION
KW - EXPRESSION
KW - INTERLEUKIN-17
KW - NEUTROPHILS
KW - COPD
KW - CYTOKINES
KW - DISTINCT
KW - MODERATE
U2 - 10.1371/journal.pone.0161433
DO - 10.1371/journal.pone.0161433
M3 - Article
C2 - 27552197
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e0161433
ER -