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 thenoncanonical NF-κB pathway and highlight an important mechanism regulating antiviral innate immunity. © 2014 Elsevier Inc.
Jin, J., Hu, H., Li, H. S., Yu, J., Xiao, Y., Brittain, G. C., … Sun, S. C. (2014). Noncanonical NF-κB pathway controls the production of type I interferons in antiviral innate immunity. Immunity, 40(3), 342–354. https://doi.org/10.1016/j.immuni.2014.02.006