New aspects of langerin dendritic cells in patients with COPD

Background: Alveolar antigen uptake has remained poorly investigated in human lungs and it is unclear to what extent dendritic cell (DC) subsets are altered in the alveolar parenchyma of patients with COPD. Objectives: To assess the distribution and marker profile of DCs in distal lungs of patients with COPD. Methods: Double/triple immunohistochemistry (IHC) for langerin, CD1a, BDCA-2, CD11c, CD68 and CD163 was performed on lung tissues from patients with GOLD stage I-IV COPD and never-smoking/smoking controls. FceRI expression on DCs was investigated by combined in situ hybridization and IHC. DCs were also assessed in mice following cigarette smoke exposure and infection with nontypeable Haemophilus influenzae (NTHi). Results: We identified four subsets of DCs; langerin + , CD1a + langerin − , BDCA-2 + , and CD11c + CD68 − CD163 − DCs. In the alveolar tissue, CD1a + langerin − (p + (p + CD68 − CD163 − DCs (p + frequently extended protrusions into the lumen. Importantly, alveolar and small airway langerin + DCs displayed site-specific phenotypes/marker profiles. Langerin + DCs also expressed high levels of high-affinity IgE receptor (FceRI) involved in cross-presentation of antigens to CD8 + T cells. To support a direct up-regulation of alveolar DCs by COPD-relevant triggers mice exposed to 3 months cigarette smoke, w/wo infection with NTHi, also had increased numbers of alveolar DCs. Conclusions: This study provides novel insights into the nature of the poorly studied alveolar DCs in distal human lungs and suggests that the alveolar region is a major arena for antigen uptake in COPD.