1. NFATC3 promotes IRF7 transcriptional activity in plasmacy--toid dendritic cells.
- Author
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Bao M, Wang Y, Liu Y, Shi P, Lu H, Sha W, Weng L, Hanabuchi S, Qin J, Plumas J, Chaperot L, Zhang Z, and Liu YJ
- Subjects
- Animals, Base Sequence, CRISPR-Cas Systems drug effects, Cell Nucleus drug effects, Cell Nucleus metabolism, Cells, Cultured, Dendritic Cells drug effects, Gene Knockdown Techniques, HEK293 Cells, Humans, Interferon Regulatory Factor-7 metabolism, Interferon Type I genetics, Interferon Type I metabolism, Mice, NFATC Transcription Factors chemistry, Oligodeoxyribonucleotides pharmacology, Promoter Regions, Genetic genetics, Protein Binding drug effects, Protein Binding genetics, Protein Domains, Protein Transport drug effects, Signal Transduction drug effects, Structure-Activity Relationship, Dendritic Cells metabolism, Interferon Regulatory Factor-7 genetics, NFATC Transcription Factors metabolism, Transcription, Genetic drug effects
- Abstract
Plasmacytoid dendritic cells (pDCs) rapidly produce large amounts of type 1 interferon (IFN) after Toll-like receptor 7 and 9 engagements. This specialized function of type 1 IFN production is directly linked to the constitutive expression of IRF7, the master transcription factor for type 1 IFN production. However, the IRF7 regulatory network in pDCs remains largely unknown. In this study, we identify that the transcription factor NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production. Furthermore, knockout of NFATC3 greatly reduced the CpG DNA-induced nuclear translocation of IRF7, which resulted in impaired type 1 IFN production in vitro and in vivo. In addition, we found that NFATC3 and IRF7 both bound to type 1 IFN promoters and that the NFAT binding site in IFN promoters was required for IRF7-mediated IFN expression. Collectively, our study shows that the transcription factor NFATC3 binds to IRF7 and functions synergistically to enhance IRF7-mediated IFN expression in pDCs., (© 2016 Bao et al.)
- Published
- 2016
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