Transcriptomics

Dataset Information

3

A role for Multidrug Resistance Protein 4 (MRP4; ABCC4) in human Dendritic Cell migration.


ABSTRACT: The capacity of dendritic cells (DC) to migrate from peripheral organs to lymph nodes (LN) is an important event in the initiation of a T cell-mediated immune response. Previously it was shown that the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the 2 multidrug resistance protein 1 (MRP1; ABCC1) 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 DC and contributes to the migratory capacity of DC. Pharmacological inhibition of MRP4 activity or down-regulation through RNAi in DC resulted in reduced migration of DC 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 PGE2, 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 molecule, significantly contributing to human DC migration towards the draining lymph nodes, and thereby relevant for the initiation of an immune response and a possible target for immunotherapy. Keywords: cell type comparison, RNAi knockdown for MRP4 2 samples were analyzed to compare. Immature DC cultured from MUTZ3 (reference control) or from MUTZ3-shMRP4 cells

ORGANISM(S): Homo sapiens  

SUBMITTER: Jelle J Lindenberg   Jean-Pierre Gillet  Anneke W Reurs  David T Curiel  Ruud Oerlemans  Rik J Scheper  Alexander Pereboev  Joel N Glasgow  Gerrit Jansen  Tanja D de Gruijl  jean-pierre gillet  George L Scheffer  Rieneke van de Ven 

PROVIDER: E-GEOD-12089 | ArrayExpress | 2008-07-12

SECONDARY ACCESSION(S): GSE12089PRJNA113525

REPOSITORIES: GEO, ArrayExpress

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Publications


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 contrib  ...[more]

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