Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human dendritic cells and monocytes treated with anti-FcgRIIb


ABSTRACT: The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies we have shown that selective antibody-mediated blockade of inhibitory FcgRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. Here we show that Fcg receptor (FcgR) mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation associated chemokines as well as type 1 interferon (IFN) response genes including the activation of signal transducer and activator of transcription 1 (STAT1). Experiment Overall Design: To further characterize FcgR mediated enhancement of DC function, we analyzed the gene expression profiles (GEP) of pure populations of monocyte-derived DCs from healthy donors (n=5) using Affymetrix Human Genome U133 Plus2.0 microarrays. Immature DCs cultured in 1% plasma were treated for 24 hours with either anti-FcgRIIB or isotype control antibody. To test whether FcgR mediated DC maturation was distinct from other maturation stimuli, we also compared DCs matured using the inflammatory cytokine cocktail (TNF-a, IL-1b, IL-6 and PGE2) commonly utilized in DC immunotherapy trials. In addition, we also treated Cd14+ monocytes (n=3) with anti-FcgRIIB antibody or isotype control. In order to better characterize the interferon responsive genes in DCs, we treated immature DCs (n=3) with 1000 U/ml of IFN-a2b.

ORGANISM(S): Homo sapiens

SUBMITTER: Kavita Dhodapkar 

PROVIDER: E-GEOD-7509 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Selective blockade of the inhibitory Fcgamma receptor (FcgammaRIIB) in human dendritic cells and monocytes induces a type I interferon response program.

Dhodapkar Kavita M KM   Banerjee Devi D   Connolly John J   Kukreja Anjli A   Matayeva Elyana E   Veri Maria Concetta MC   Ravetch Jeffrey V JV   Steinman Ralph M RM   Dhodapkar Madhav V MV  

The Journal of experimental medicine 20070514 6


The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies, we have shown that selective antibody-mediated blockade of inhibitory FcgammaRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. We show that Fcgamma receptor (FcgammaR)-mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene express  ...[more]

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