A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration

Rieneke Van De Ven, George L. Seheffer, Anneke W. Reurs, Jelle J. Lindenberg, Ruud Oerlemans, Gerrit Jansen, Jean Pierre Gillet, Joel N. Glasgow, Alexander Pereboev, David T. Curiel, Rik J. Scheper, Tanja D. De Gruijl

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The capacity of dendritic cells (DCs) to migrate from peripheral organs to lymph nodes (LNs) is important in the initiation of a T cell-mediated immune response. The ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the multidrug resistance protein 1 (MRP1; ABCC1) have been shown to play a role in both human and murine DC migration. Here we show that a more recently discovered family member, MRP4 (ABCC4), is expressed on both epidermal and dermal human skin DCs and contributes to the migratory capacity of DCs. Pharmacological inhibition of MRP4 activity or downregulation through RNAi in DCs resulted in reduced migration of DCs from human skin explants and of in vitro generated Langerhans cells. The responsible MRP4 substrate remains to be identified as exogenous addition of MRP4's known substrates prostaglandin E 2, leukotriene B4 and D4, or cyclic nucleotides (all previously implicated in DC migration) could not restore migration. This notwithstanding, our data show that MRP4 is an important protein, significantly contributing to human DC migration toward the draining lymph nodes, and therefore relevant for the initiation of an immune response and a possible target for immunotherapy.

Original languageEnglish
Pages (from-to)2353-2359
Number of pages7
JournalBlood
Volume112
Issue number6
DOIs
StatePublished - Sep 15 2008

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