Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties

Upon exposure to immune or inflammatory stimuli, dendritic cells (DC) migrate from peripheral tissues to lymphoid organs, where they present Ag. CC chemokines induce chemotactic and transendothelial migration of immature DC, in vitro. Maturation of DC by CD40L, or by LPS, IL-1, and TNF, induces down-regulation of the two main CC chemokine receptors expressed by these cells, CCR1 and CCRS, and abrogates chemotaxis to their ligands. Inhibition was rapid (<1 h) and included the unrelated agent FMLP. Concomitantly, the expression of CCR7 and the migration to its ligand EBI1 ligand chemokine (ELC)/macrophage inflammatory protein (MIP)-3beta, a chemokine expressed in lymphoid organs, were strongly up-regulated, though with slower kinetics (24-48 h). Rapid inhibition of responsiveness to chemoattractants present at sites of inflammation and immune reaction may be permissive for leaving peripheral tissues. Conversely, the slower acquisition of responsiveness to ELC/MIP-3beta may guide subsequent localization of DC in lymphoid organs.