Localization and trafficking of pulmonary dendritic cells during early stages of airway inflammation

Abstract

Abstract Pulmonary dendritic cells (DCs) take up inhaled antigens, migrate to draining lymph nodes (LNs), and stimulate antigen-specific T cells. Bona fide pulmonary DCs (CD11c+CD88−) comprise CD103+ and CD11b/CD172a+ subsets, and their migration from lung to LNs is directed by the chemokine receptor, CCR7. However, the precise localization of these two different DC subsets in the lung, and how they move during the early stage of inflammation, are largely unknown. In this study, using multi-color high resolution imaging of precision cut lung slices, we found that at steady state, both CD103+ and CD172a+ DCs reside immediately adjacent to airways lined with CD324/E-cadherin-expressing epithelial cells. Interestingly, this region of the airways is also closely associated with lymphatic vessels, whereas regions lacking CD324 are not associated with either DCs or lymphatic vessels. Inhalation of LPS induced a Ccr7-gfp reporter gene within 2 h post-exposure, but the DCs remained closely associated with airways. By 6 h post- exposure, the number of airway-associated DCs decreased, while DCs associated with lymphatic vessels significantly increased. Very few DCs were detected in lung parenchyma. These observations suggest that after sensing danger signals, DCs translocate directly from the airway to lymphatics without first transiting through the parenchyma. In agreement with this rapid migration, activation of antigen-specific T cells was detected in regional LNs within 6 h of exposure.