Chemokines and dendritic cell traffic

Localization in tissues and migration to lymphoid organs are essential steps in the immunobiology of dendritic cells (DC). Chemokines play an important role in guiding the traffic of DC. Receptor expression and responsiveness to constitutively made chemokines account for the presence of DC in normal tissues. Inflammatory chemokines and nonchemokine attractants promote recruitment and localization of DC at sites of inflammation and infection. Upon exposure to maturation signals, DC undergo a chemokine receptor switch, with down-regulation of inflammatory chemokine receptors followed by induction of CCR7. These temporally coordinated events allow DC to leave tissues and to localize in lymphoid organs by responding to CCR7 agonists. DC are also present in tumors that produce chemokines, but their significance remains to be defined. In addition to responding to chemokines, DC are a major source of certain chemokines such as macrophage-derived chemokine. The interaction of DC with chemokines is essential to the function of these cells in normal and pathological conditions and may provide tools for novel therapeutic strategies.