Chest
Volume 139, Issue 5, May 2011, Pages 1089-1100
Journal home page for Chest

Original Research
COPD
Identification of Cells Expressing IL-17A and IL-17F in the Lungs of Patients With COPD

https://doi.org/10.1378/chest.10-0779Get rights and content

Background

Lymphocytes secrete IL-17A and IL-17F, which enhance innate immune responses. IL-17 expression has not been studied in COPD small airways. The aim of this study was to quantify IL-17A and IL-17F expression in the peripheral lung tissue of patients with COPD compared with control subjects and to identify inflammatory cells that express IL-17.

Methods

IL-17 expression was assessed using immunohistochemistry in peripheral lung tissue (18 patients with COPD and 10 smokers and 10 nonsmokers with normal lung function) and induced sputum (12 patients with COPD and six nonsmokers). Alveolar macrophages from eight patients with COPD, eight smokers, and seven nonsmokers were used for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.

Results

The number of inflammatory cells expressing IL-17A in the small airway subepithelium was higher in patients with COPD than in smokers (P = .01) and nonsmokers (P = .02). IL-17A expression was higher than IL-17F in this region. IL-17A was expressed by lymphocytes, neutrophils, and macrophages (confirmed by RT-PCR). The expression of IL-17F was greater than IL-17A in epithelial cells and lymphoid follicles, although there were no differences among subject groups.

Conclusions

Our findings indicate different roles for IL-17A and IL-17F in the pathogenesis of COPD. IL-17A plays a role in small airway subepithelial inflammation, whereas IL-17F appears to play a more prominent role within lymphoid follicles.

Section snippets

Study Subjects

Thirty-eight patients undergoing surgical resection for suspected or confirmed lung cancer were recruited for immunohistochemistry studies (Table 1). A different group of 25 patients undergoing surgery were recruited for gene expression studies using alveolar macrophages (Table 2). Twelve patients with COPD and six nonsmoking control subjects were recruited for induced sputum studies (Table 3). Patients with COPD were diagnosed according to GOLD (Global Initiative for Chronic Obstructive Lung

Subepithelial IL-17 Expression

In peripheral lung tissue specimens, IL-17A expression was observed in the infiltrating cells in the subepithelial regions of almost every small airway examined in all three subject groups. Examples of IL-17A subepithelial expression within lung tissue from patients with COPD, smokers, and nonsmokers are presented in Figures 1A-C The number of IL-17A immunoreactive subepithelial cells per square millimeter was increased in patients with COPD compared with control subjects (ANOVA P = .01; COPD

Discussion

We observed increased IL-17A expression in infiltrating inflammatory cells in the subepithelium of the small airways of patients with COPD compared with control subjects. We also observed that IL-17A expression was greater than IL-17F expression in the subepithelial region and that IL-17A was expressed by inflammatory cells other than lymphocytes, including neutrophils and macrophages. In contrast, at other anatomic locations, including the epithelial region, alveolar walls, and lymphoid

Acknowledgments

Author contributions: Dr Eustace: contributed intellectual and technical input to the study design and manuscript preparation.

Dr Smyth: contributed intellectual and technical input to the study design and manuscript preparation.

Ms Mitchell: contributed to the technical work and analysis of the study and review of the manuscript.

Ms Williamson: contributed to the technical work and analysis of the study and review of the manuscript.

Dr Plumb: contributed intellectual and technical input to the

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    Funding/Support: This study was funded by an unrestricted research grant from UCB Celltech Ltd.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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