The leukotriene C-4 transporter MRP1 regulates CCL19 (MIP-3 beta, ELC)-dependent mobilization of dendritic cells to lymph nodes

Adaptive immune responses begin after antigen-bearing dendritic cells (DCs) traffic from peripheral tissues to lymph nodes. Here, we show that DC migr ation from skin to lymph nodes utilizes the leukotriene C-4 (LTC4) transpor ter multidrug resistance-associated protein 1 (MRP1). DC mobilization from the epidermis and trafficking into lymphatic vessels was greatly reduced in MRP1(-/-) mice, but migration was restored by exogenous cysteinyl leukotri enes LTC4 or LTD,. In vitro, these cysteinyl leukotrienes promoted optimal chemotaxis to the chemokine CCL19, but not to other related chemokines. Ant agonism of CCL19 in vivo prevented DC migration out of the epidermis. Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LT C4, which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis.