Selected natural and synthetic retinoids impair CCR7- and CXCR4-dependent cell migration in vitro and in vivo

Dendritic cell (DC) migration to sec- ondary lymphoid organs is a crucial step to initiate adaptive immune responses. This step requires the expression of a functional CCR7 chemokine recep- tor on DC undergoing maturation. Here, we show that the natural retinoid 9-cis retinoic acid (9cRA) and the synthetic retinoid fenretinide (4-HPR) spe- cifically inhibit the functional up-regulation of CCR7 on maturing human DCs, without affecting early steps of DC maturation. As a consequence, mature DCs do not migrate in vitro toward the chemokine CCL19. Importantly, 4-HPR and 9cRA by inhibiting the expression of CCR7 on bone mar- row-derived murine DCs dampen their in vivo mi- gration to draining lymph nodes. 4-HPR also inhib- its the expression of the chemokine receptors CXCR4, therefore, impairing in vitro migration of human DCs to CXCL12 and inhibiting in vivo the CXCR4-dependent migration of the posterior lat- eral line primordium (PLLp) in zebrafish embryos. Taken together, these data highlight a novel func- tion of retinoids and suggest the possibility of using retinoids to treat inflammatory or autoimmune diseases. J. Leukoc. Biol. 84: 000-000; 2008.