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Immunity. 2014 Mar 20;40(3):342-54. doi: 10.1016/j.immuni.2014.02.006.

Noncanonical NF-κB pathway controls the production of type I interferons in antiviral innate immunity.

Author information

1
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Medicine, University of Montreal, Montreal, QC H1T 2M4, Canada.
3
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.
4
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.

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.

PMID:
24656046
PMCID:
PMC3983709
DOI:
10.1016/j.immuni.2014.02.006
[Indexed for MEDLINE]
Free PMC Article

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