Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17+ Cells in Asthmatic Airways.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Asthma/*drug therapy ; Inflammation/*drug therapy ; Interleukin-17/*genetics ; Respiratory Therapy/*adverse effects; Adrenal Cortex Hormones/administration & dosage ; Adrenal Cortex Hormones/adverse effects ; Adult ; Asthma/genetics ; Asthma/immunology ; Asthma/pathology ; Biopsy ; Bronchi/drug effects ; Bronchi/pathology ; Cell Lineage/genetics ; Cell Lineage/immunology ; Eosinophils/drug effects ; Eosinophils/immunology ; Female ; Gene Expression Regulation ; Humans ; Hypersensitivity, Immediate/chemically induced ; Hypersensitivity, Immediate/immunology ; Hypersensitivity, Immediate/pathology ; Inflammation/immunology ; Inflammation/pathology ; Interleukin-17/immunology ; Male ; Middle Aged ; Neutrophils/drug effects ; Neutrophils/immunology ; Th17 Cells/immunology

Background: Interleukin (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.
Methods: Bronchial 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.
Results: In 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.
Conclusions: We 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.
Competing Interests: The authors have declared that no competing interests exist.

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0 (Adrenal Cortex Hormones)
0 (Interleukin-17)

Date Created: 20160824 Date Completed: 20170727 Latest Revision: 20181113

20240829

PMC4994949

10.1371/journal.pone.0161433

27552197