NFATC3 promotes IRF7 transcriptional activity in plasmacy–toid dendritic cells.
Yong-Jun Liu M.D.
Bao, M., Y. Wang, Y. Liu, P. Shi, H. Lu, W. Sha, L. Weng, S. Hanabuchi, J. Qin, J. Plumas, L. Chaperot, Z. Zhang and Y. J. Liu (2016). “Nfatc3 promotes irf7 transcriptional activity in plasmacy–toid dendritic cells.” J Exp Med 213(11): 2383-2398.
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.