Unique Regulation of CCL18 Production by Maturing Dendritic Cells

Dendritic cells (DC) orchestrate the trafficking of lymphocytes by secreting chemokines with different specificity and function. Chemokines are produced at higher levels by mature DC. This study shows that CCL18 is one of the most abundant chemokines produced by immature DC. In contrast to all other chemokines investigated to date, CCL18 was selectively down-regulated during the maturation process induced by LPS, TNF, CD40 ligand, Staphylococcus aureus Cowan I, Candida albicans, and influenza virus. IL-10 and vitamin D(3), two known inhibitors of DC differentiation and function, strongly promoted CCL18 secretion, whereas IFN-gamma, a costimulator of DC function, inhibited its production. IL-10 also induced CCL18 secretion in blood myeloid DC. No CCL18 secretion was observed in blood plasmacytoid DC. The opposite pattern of regulation was observed for CCL20, a prototypic inflammatory chemokine. CCL18 was found to be a chemotactic factor for immature DC. Therefore, CCL18 may act as a chemotactic signal that promotes the colocalization of immature DC with naive T lymphocytes in an IL-10-dominated environment with the consequent generation of T regulatory cells. These characteristics suggest that CCL18 may be part of an inhibitory pathway devoted to limiting the generation of specific immune responses at peripheral sites.