The Leukotriene C4 Transporter MRP1 Regulates CCL19 (MIP-3β, ELC)–Dependent Mobilization of Dendritic Cells to Lymph Nodes

TLDR

Adaptive immune responses begin after antigen‑bearing dendritic cells traffic from peripheral tissues to lymph nodes. The study demonstrates that the leukotriene C4 transporter MRP1 is essential for dendritic cell migration from the epidermis to lymph nodes, acting through LTC4‑mediated chemotaxis to CCL19, as MRP1‑deficient mice show impaired migration that is rescued by exogenous LTC4/LTD4 and blocked by CCL19 antagonism.

Abstract

Adaptive immune responses begin after antigen-bearing dendritic cells (DCs) traffic from peripheral tissues to lymph nodes. Here, we show that DC migration from skin to lymph nodes utilizes the leukotriene C4 (LTC4) transporter 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 leukotrienes LTC4 or LTD4. In vitro, these cysteinyl leukotrienes promoted optimal chemotaxis to the chemokine CCL19, but not to other related chemokines. Antagonism of CCL19 in vivo prevented DC migration out of the epidermis. Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LTC4, which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis.