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Accumulation of Dendritic Cells and Increased CCL20 Levels in the Airways of Patients with Chronic Obstructive Pulmonary Disease

¹ Department of Respiratory Diseases, Ghent University Hospital, Ghent; ² Department of Respiratory Diseases, Leuven University Hospital, Leuven; and ³ Department of Thoracic and Vascular Surgery, Ghent University Hospital, Ghent, Belgium

Correspondence and requests for reprints should be addressed to Ingel K. Demedts, Department of Respiratory Diseases, Ghent University Hospital 7K12IE, De Pintelaan 185, B-9000 Ghent, Belgium. E-mail M.DemedtsIngelK{at}UGent.be

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process.

Objectives: To evaluate the presence of DC in small airways of patients with COPD.

Methods: We evaluated DC infiltration in small airways by immunohistochemistry in patients with COPD (stage I-IV), never-smokers, and smokers without COPD. Chemokine ligand 20 (CCL20, the most potent chemokine in attracting DC) was determined in total lung by RT-PCR and in induced sputum by enzyme-linked immunsorbent assay. Chemokine receptor 6 (CCR6, the receptor for CCL20) expression on human pulmonary DC was evaluated by RT-PCR and flow cytometry.

Measurements and Main Results: There is a significant increase in DC number in the epithelium (p = 0.007) and adventitia (p = 0.009) of small airways of patients with COPD compared with never-smokers and smokers without COPD. DC number in epithelium and adventitia increases along with disease severity. CCL20 mRNA expression in total lung and CCL20 protein levels in induced sputum are significantly higher in patients with COPD compared with never-smokers (p = 0.034 for CCL20 mRNA and p = 0.0008 for CCL20 protein) and smokers without COPD (p = 0.016 for CCL20 mRNA and p = 0.001 for CCL20 protein). DC isolated from human lung express CCR6 both at mRNA and at protein level.

Conclusions: This is the first description of airway infiltration by DC in COPD. Moreover, interaction between CCL20 and CCR6 provides a possible mechanism for accumulation of DC in the lungs in COPD.

Key Words: langerin • CCL20 • CCR6

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Macrophages, neutrophils, and CD8+ T cells participate in this inflammatory process. It is unclear if dendritic cells (DC) are involved in the chronic airway inflammation in COPD. What This Study Adds to the Field There is accumulation of DC in COPD airways, which increases with disease severity. It is demonstrated that CCL20 (the most important chemokine for attracting DC) is elevated in COPD lungs and DC express CCR6 (receptor for CCL20).