title: Noncanonical NF-κB pathway controls the production of type I interferons in antiviral innate immunity.
abstract: Production of type I interferons (IFN-I) is a crucial innate immune mechanism against viral infections. IFN-I induction is subject to negative regulation by both viral and cellular factors, but the underlying mechanism remains unclear. We report that the noncanonical NF-κB pathway was stimulated along with innate immune cell differentiation and viral infections and had a vital role in negatively regulating IFN-I induction. Genetic deficiencies in major components of the noncanonical NF-κB pathway caused IFN-I hyperinduction and rendered cells and mice substantially more resistant to viral infection. Noncanonical NF-κB suppressed signal-induced histone modifications at the Ifnb promoter, an action that involved attenuated recruitment of the transcription factor RelA and a histone demethylase, JMJD2A. These findings reveal an unexpected function of the noncanonical NF-κB pathway and highlight an important mechanism regulating antiviral innate immunity.
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Haiyan S
authors.initials: HS
authors.lastname: Li
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Brittain
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Medicine, University of Montreal, Montreal, QC H1T 2M4, Canada.
authors.forename: Frédérick A
authors.initials: FA
authors.lastname: Mallette
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Watowich
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. Electronic address: ssun@mdanderson.org.
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D007370:Interferon Type I / Q000096:biosynthesis*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D016298:Hematopoietic Cell Growth Factors; D056466:Histone Demethylases; D006657:Histones; D007370:Interferon Type I; D016899:Interferon-beta; D008024:Ligands; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D000097782:NF-kappaB-Inducing Kinase; C560307:JMJD2A protein, mouse