Migratory properties of pulmonary dendritic cells are developmentally programmed (61.4)

Abstract

Abstract Pulmonary dendritic cells (DCs) take up inhaled allergens and migrate to draining lymph nodes (LN) to present antigens to naïve T cells. However, pulmonary DCs are also required to elicit inflammation after allergen challenge, suggesting the presence of both migratory and non-migratory DCs. There are two phenotypically distinct major lung DC subsets, defined by their expression of CD103 and CD11b, respectively. We used a novel Ccr7-gfp knock-in reporter mouse to study Ccr7 expression in lung DCs. Ccr7-gfp was expressed in many CD103 DCs, but in few CD11bhi DCs. Using the dye PKH26 to track lung DCs, we found that many CD103+ DCs migrate to draining LNs, whereas relatively few CD11bhi DCs do so. Thus, CD11bhi lung DCs are comprised of both migratory and non-migratory cells. Further analysis revealed that monocyte-derived (mo)CD14hi CD11bhi DCs, including LPS-elicited Ly-6Chi inflammatory DCs, do not express Ccr7 or migrate to LNs. Flt3l-/- mice, which lack DCs derived from the common DC precursor (CDP) but retain moDCs, possessed almost no migratory Ccr7-expressing DCs in the lung. Conversely, mice lacking both Ccr2 and Cx3cr1 lacked moDCs, but retained migratory, CDP-derived DCs. These findings show that the migratory activity of CD11bhi DCs is developmentally programmed; CDP-derived CD103+ and CD11bhi pulmonary DCs are migratory, whereas monocyte-derived CD11bhi DCs do not express Ccr7 and therefore remain in the lung, even during acute pulmonary inflammation.