Delta opioid receptors mediate chemotaxis in bone marrow-derived dendritic cells

Abstract

Endogenous opioid peptides are locally produced at the inflammatory site where antigens are captured and processed by dendritic cells (DCs). Subsequently, maturing DCs migrate towards draining lymph nodes to initiate T cell response. Given the primordial role of DCs in adaptive immune response, we examined whether opioids may affect the migratory response of DCs. We found that the delta opioid receptor (DOR) mRNA was expressed at low level in bone marrow-derived immature DCs and up-regulated upon DC maturation. Moreover, DOR agonists triggered DC chemotaxis in vitro. In vivo, enkephalins prevented the egress of mature DCs injected into the peritoneal cavity of normal mice. This effect was inhibited by blocking opioid receptors on mature DCs. The cross-talk between CCR7 and DOR receptors that are both up-regulated during DC maturation was then examined. Whereas opioids did not alter the migratory responsiveness to CCR7 ligands, DOR-mediated mobilization of mature DCs was inhibited by CCL19 and CCL21 suggesting that the opioid chemotactic activity decreases as the concentration of the chemokines increases.