The leukotriene C4 transporter MRP1 regulates CCL19 (MIP-3β, ELC)-dependent mobilization of dendritic cells to lymph nodes

Davide F. Robbiani, Rick A. Finch, Dirk Jäger, William A. Muller, Alan C. Sartorelli, Gwendalyn J. Randolph*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

405 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)757-768
Number of pages12
JournalCell
Volume103
Issue number5
DOIs
StatePublished - Nov 22 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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