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| Status |
Public on Nov 30, 2016 |
| Title |
Transcriptional repression of IRF7 by MYC is critical for antiviral immune response in human pDC [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Type I interferons (IFN) are crucial mediators of human innate and adaptive immunity and are massively produced from plasmacytoid dendritic cells (pDC). IRF7 is a critical regulator of type I IFN production when pathogens are detected by TLR7/9 in pDC. However, hyperactivation of pDC can cause life-threatening autoimmune diseases. To avoid the deleterious effects of aberrant pDC activation, tight regulation of IRF7 is required. Nonetheless, the detailed mechanisms of how IRF7 transcription is regulated in pDC are still elusive. To this end, we identified the global gene expression changes after stimulation of human primary pDC with the TLR9 agonist CpGB. We identified that the transcription factor MYC is prominently upregulated upon CpGB engagement in pDC. Moreover, when we knocked down MYC in the pDC-like cell line GEN2.2, production of interferon-stimulated genes (ISGs) was dramatically increased and was further enhanced by CpGB. Interestingly, MYC is shown to be recruited to the IRF7 promoter region through interaction with NCOR2/HDAC3 for its repression, and HDAC3 inhibition enhanced IRF7 expression and IFNβ production. Interestingly, activation of TLR9-mediated NF-kB and MAPK and nuclear translocation of IRF7 were greatly enhanced by MYC depletion. Pharmaceutical inhibition of MYC recovered IRF7 expression, further confirming the negative role of MYC in the antiviral response by pDC. Furthermore, the inverse correlation of MYC and IRF7 was validated in psoriasis skin sample datasets. Therefore, our results identify the novel immunomodulatory role of MYC in human pDC and may add to our understanding of aberrant pDC function in autoimmune diseases.
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| Overall design |
1 sample unstimulated GEN2.2 cells with 2 μg of anti-MYC antibody; 1 sample unstimulated GEN2.2 cells with 2 μg of rabbit IgG control antibody.
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| Contributor(s) |
Kim TW, Hong S, Lin Y, Joo H, Kim T, Pascual V, Liu Y |
| Citation(s) |
27630164 |
| Submission date |
Jun 25, 2015 |
| Last update date |
Mar 16, 2023 |
| Contact name |
Nicole Baldwin |
| E-mail(s) |
Nicole.Baldwin@BSWHealth.org
|
| Organization name |
Baylor Research Institute
|
| Street address |
3434 Live Oak St
|
| City |
Dallas |
| ZIP/Postal code |
75204 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE70278 |
Transcriptional repression of IRF7 by MYC is critical for antiviral immune response in human pDC |
|
| Relations |
| BioProject |
PRJNA288145 |
| SRA |
SRP059881 |
