title: NFATC3 promotes IRF7 transcriptional activity in plasmacy--toid 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 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.
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.|MedImmune, LLC, Gaithersburg, MD 20878.
authors.forename: Musheng
authors.identifier: 0000-0002-3567-6583
authors.initials: M
authors.lastname: Bao
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.|MedImmune, LLC, Gaithersburg, MD 20878.
authors.forename: York
authors.identifier: 0000-0002-0077-0772
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.
authors.forename: Ying
authors.identifier: 0000-0002-6343-2498
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.
authors.forename: Peiqing
authors.identifier: 0000-0002-4526-7484
authors.initials: P
authors.lastname: Shi
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.|MedImmune, LLC, Gaithersburg, MD 20878.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Lu
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.|MedImmune, LLC, Gaithersburg, MD 20878.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Sha
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.|MedImmune, LLC, Gaithersburg, MD 20878.
authors.forename: Leiyun
authors.identifier: 0000-0003-2438-577X
authors.initials: L
authors.lastname: Weng
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204.|MedImmune, LLC, Gaithersburg, MD 20878.
authors.forename: Shino
authors.initials: S
authors.lastname: Hanabuchi
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Etablissement Français du Sang Rhone-Alpes, 38701 La Tronche, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Plumas
authors.affiliation: Etablissement Français du Sang Rhone-Alpes, 38701 La Tronche, France.
authors.forename: Laurence
authors.identifier: 0000-0002-1479-9410
authors.initials: L
authors.lastname: Chaperot
authors.affiliation: Immunobiology and Transplant Research, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204 yjliuanderson@yahoo.com.|MedImmune, LLC, Gaithersburg, MD 20878.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics* / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050778:NFATC Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D000072417:Protein Domains; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C408982:CPG-oligonucleotide; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494235:Irf7 protein, mouse; D050778:NFATC Transcription Factors; D009838:Oligodeoxyribonucleotides; C445503:transcription factor NF-AT c3