Cutting Edge: Differential Regulation of Chemokine Receptors During Dendritic Cell Maturation: A Model for Their Trafficking Properties

TLDR

Immune or inflammatory stimuli trigger dendritic cells to migrate from peripheral tissues to lymphoid organs, where CC chemokines promote chemotaxis and transendothelial migration of immature DC. DC maturation via CD40L, LPS, IL‑1, or TNF rapidly (<1 h) down‑regulates CCR1/CCR5 and abolishes chemotaxis to CC chemokines, while gradually (24–48 h) up‑regulating CCR7 and responsiveness to ELC/MIP‑3β, thereby facilitating exit from peripheral tissues and subsequent homing to lymphoid organs.

Abstract

Abstract 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 CCR5, and abrogates chemotaxis to their ligands. Inhibition was rapid (&amp;lt;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)-3β, 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-3β may guide subsequent localization of DC in lymphoid organs.