Noncanonical NF-κB Pathway Controls the Production of Type I Interferons in Antiviral Innate Immunity
| Autor: | Shao Cong Sun, Hongbo Hu, Jiayi Yu, George C. Brittain, Qiang Zou, Stephanie S. Watowich, Frédérick A. Mallette, Haiyan S. Li, Jin Jin, Yichuan Xiao, Xuhong Cheng |
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| Rok vydání: | 2014 |
| Předmět: |
Cellular differentiation
Immunology Protein Serine-Threonine Kinases Hematopoietic Cell Growth Factors Ligands Article Histones 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals Immunology and Allergy Promoter Regions Genetic 030304 developmental biology Regulation of gene expression Histone Demethylases 0303 health sciences Innate immune system biology Toll-Like Receptors NF-kappa B Transcription Factor RelA NF-κB Cell Differentiation Dendritic Cells Interferon-beta NFKB1 Immunity Innate 3. Good health Cell biology Enzyme Activation Histone Infectious Diseases chemistry Gene Expression Regulation Virus Diseases 030220 oncology & carcinogenesis Interferon Type I biology.protein Demethylase Female Interferon type I medicine.drug Protein Binding |
| Zdroj: | Immunity. 40(3):342-354 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2014.02.006 |
| Popis: | SummaryProduction 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. |
| Databáze: | OpenAIRE |
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