Migratory properties of pulmonary dendritic cells are determined by their developmental lineage.

Abstract

The chemokine receptor, CCR7, directs the migration of dendritic cells (DCs) from peripheral tissue to draining lymph nodes (LNs). However, it is unknown whether all pulmonary DCs possess migratory potential. Using novel Ccr7(gfp) reporter mice, we found that Ccr7 is expressed in CD103⁺ and a CD14(med/lo) subset of CD11b(hi) classical (c)DCs but not in monocyte-derived (mo)DCs, including Ly-6C(hi)CD11b(hi) inflammatory DCs and CD14(hi)CD11b(hi) DCs. Consequently, cDCs migrated to lung-draining LNs but moDCs did not. Mice lacking the chemokine receptor, CCR2, also lacked inflammatory DCs in the lung after lipopolysaccharide inhalation but retained normal levels of migratory DCs. Conversely, the lungs of fms-like tyrosine kinase 3 ligand (Flt3L)-deficient mice lacked cDCs but retained moDCs, which were functionally mature but did not express Ccr7 and were uniformly non-migratory. Thus, the migratory properties of pulmonary DCs are determined by their developmental lineage.