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E-GEOD-70429 - IRF-5 and IRF-8 govern the response of Human Plasmacytoid Dendritic Cells following TLR9 ligation

Status
Released on 1 June 2016, last updated on 4 June 2016
Organism
Homo sapiens
Samples (48)
Array (1)
Protocols (35)
Description
Synthetic oligonucleotides (ODNs) containing CpG motifs stimulate human plasmacytoid dendritic cells (pDCs) to produce type-1 interferons (IFN) and pro-inflammatory cytokines. Previous studies demonstrated that interferon regulatory factors (IRFs) played a central role in mediating CpG-induced pDC activation. This work explores the inverse effects of IRF-5 and IRF-8 on CpG dependent gene expression. Results from RNA interference and microarray studies indicate that IRF-5 up-regulates TLR9-driven gene expression whereas IRF-8 down-regulates the same genes. Several findings support the conclusion that IRF-8 inhibits TLR9 dependent gene expression by directly blocking the activity of IRF-5. First, the inhibitory activity of IRF-8 is only observed when IRF-5 is present. Second, proximity ligation analysis shows that IRF-8 and IRF-5 co-localize within the cytoplasm of resting human pDC and co-translocate to the nucleus after CpG stimulation. Taken together, these findings suggest that two transcription factors with opposing functions control TLR9 signaling in human pDCs. CAL-1 cells were transfected with siRNA targeting IRF-5 (IRF-5si) and left unstimulated (n=4, technical repeats) or stimulated with K-type CpG ODN (n=4, technical repeats). CAL-1 cells were transfected with siRNA targeting IRF-8 (IRF-8si) and left unstimulated (n=4, technical repeats) or stimulated with K-type CpG ODN (n=4, technical repeats). CAL-1 cells were transfected with control siRNA (Contsi) and left unstimulated (n=4, technical repeats) or stimulated with K-type CpG ODN (n=4, technical repeats).
Experiment type
transcription profiling by array 
Contact
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-70429.idf.txt
Sample and data relationshipE-GEOD-70429.sdrf.txt
Raw data (1)E-GEOD-70429.raw.1.zip
Processed data (1)E-GEOD-70429.processed.1.zip
Array designA-GEOD-20644.adf.txt
Links