EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-κB Activation

6533b82ffe1ef96bd12951b6

RESEARCH PRODUCT

EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-κB Activation

Stefan Wirtz Christoph Becker Markus F. Neurath Edward E. S. Nieuwenhuis Mark Birkenbach Massimo Fantini Ingrid Tubbe Hans Schild Richard S. Blumberg Peter R. Galle

subject

RNA Caps medicine.medical_treatment DNA Mutational Analysis Molecular Sequence Data Immunology Antigen-Presenting Cells Receptors Cell Surface Biology Cell Line Minor Histocompatibility Antigens Jurkat Cells Mice Cell Line Tumor Gene expression medicine Animals Humans Immunology and Allergy Receptors Cytokine Promoter Regions Genetic Glycoproteins Mice Knockout Membrane Glycoproteins Innate immune system Base Sequence Toll-Like Receptors HEK 293 cells NF-kappa B TLR9 hemic and immune systems EBI3 Dendritic Cells Molecular biology Toll-Like Receptor 2 Up-Regulation Mice Inbred C57BL Toll-Like Receptor 4 Protein Subunits TLR2 Cytokine Gene Expression Regulation Toll-Like Receptor 9 NIH 3T3 Cells TLR4 Protein Binding Signal Transduction

description

Abstract The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of the cytokine IL-27 that controls Th cell development. However, its regulated expression in DCs is poorly understood. In the present study we demonstrate that EBI3 is expressed in splenic CD8−, CD8+, and plasmacytoid DC subsets and is induced upon TLR signaling. Cloning and functional analysis of the EBI3 promoter using in vivo footprinting and mutagenesis showed that stimulation via TLR2, TLR4, and TLR9 transactivated the promoter in primary DCs via NF-κB and Ets binding sites at −90 and −73 bp upstream of the transcriptional start site, respectively. Furthermore, we observed that NF-κB p50/p65 and PU.1 were sufficient to transactivate the EBI3 promoter in EBI3-deficient 293 cells. Finally, induced EBI3 gene expression in DCs was reduced or abrogated in TLR-2/TLR4, TLR9, and MyD88 knockout mice, whereas both basal and inducible EBI3 mRNA levels in DCs were strongly suppressed in NF-κB p50-deficient mice. In summary, these data suggest that EBI3 expression in DCs is transcriptionally regulated by TLR signaling via MyD88 and NF-κB. Thus, EBI3 gene transcription in DCs is induced rapidly by TLR signaling during innate immune responses preceding cytokine driven Th cell development.

year	journal	country	edition	language
2005-02-25	The Journal of Immunology

https://doi.org/10.4049/jimmunol.174.5.2814