NFATC3 promotes IRF7 transcriptional activity in plasmacytoid dendritic cells

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 NFA TC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production. Furthermore, knockout of NFA TC3 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 NFA TC3 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 NFA TC3 binds to IRF7 and functions synergistically to enhance IRF7-mediated IFN expression in pDCs.