Expansion of Phenotypically Altered Dendritic Cell Populations in the Small Airways and Alveolar Parenchyma in Patients with Chronic Obstructive Pulmonary Disease

Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex immunohistochemistry was applied to quantify langerin/CD207⁺, CD1a⁺, BDCA2⁺, and CD11c⁺ subsets in distal lung compartments from patients with COPD (GOLD stage I–IV) and never-smoking and smoking controls. In the alveolar parenchyma, increased numbers of CD1a⁺langerin⁻ (p < 0.05) and BDCA-2⁺ DCs (p < 0.001) were observed in advanced COPD compared with controls. Alveolar CD11c⁺ DCs also increased in advanced COPD (p < 0.01). In small airways, langerin⁺ and BDCA-2⁺ DCs were also significantly increased. Contrasting the small airway DCs, most alveolar DC subsets frequently extended luminal protrusions. Importantly, alveolar and small airway langerin⁺ DCs in COPD lungs displayed site-specific marker profiles. Further, multiplex immunohistochemistry with single-cell quantification was used to specifically profile langerin DCs and reveal site-specific expression patterns of the maturation and activation markers S100, fascin, MHC2, and B7. Taken together, our results show that clinically advanced COPD is associated with increased levels of multiple alveolar DC populations exhibiting features of both adaptive and innate immunity phenotypes. This expansion is likely to contribute to the distal lung immunopathology in COPD patients.