Complex alterations of lung dendritic cell subsets across distinct asthma phenotypes

Abstract

Rationale: Whether antigen presenting dendritic cell (DC) subsets are differently altered across asthma phenotypes remains unknown. This study explores multiple DC subsets in bronchial and alveolar tissues from patients with different phenotypes of asthma.

Methods: Endobronchial biopsies (n=185) were obtained from healthy controls (n=8), patients with mild-moderate controlled (n=12) or uncontrolled (n=12) atopic asthma, and severe asthma (n=25). Transbronchial biopsies (n = 160) were obtained from healthy controls and mild-moderate asthmatics. Automatized immunohistochemistry was used for visualizing DC identification markers (CD1a, langerin, CD11c, BDCA2), confounding non-DCs (CD68, CD163), and DC phenotype markers (S-100, CD83 and RUNX3). Analysis was performed by tissue slide scanning techniques and computerized image analysis.

Results: In healthy controls, langerin⁺ and CD11c⁺CD68^-CD163^- DCs were the most frequent DC populations within the bronchi. Epithelial langerin⁺ DCs decreased in severe asthmatics compared with controls (p<0.01). Severe asthma was also associated with lower numbers of subepithelial CD11c⁺CD68^-CD163^-DCs (p<0.01) and BDCA2⁺ DCs (p<0.01). Numbers of bronchial CD11c⁺CD68^-CD163^- DCs decreased in controlled asthmatics compared with controls (p<0.05) whereas decreased alveolar CD11c⁺CD68^-CD163^- DC levels were decreased in uncontrolled asthmatics (p<0.001).

Conclusions: This study shows that DC subsets are differentially altered in asthmatic patients and where severe asthma is associated with a particularly marked DC reduction which is likely caused by the high doses of steroids in this patient group.