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    Pellino3 targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons


    Siednienko, Jakcub and Jackson, Ruaidhri and Mellett, Mark and Delagic, Nezira and Yang, Shuo and Wang, Bingwei and Tang, Lisa S. and Callanan, John J. and Mahon, Bernard P. and Moynagh, Paul N. (2012) Pellino3 targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons. Nature Immunology, 13. pp. 1055-1062. ISSN 1529-2908

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    Abstract

    Toll-like receptors (TLRs) sense pathogen-associated molecules and respond by inducing cytokines and type I interferon. Here we show that genetic ablation of the E3 ubiquitin ligase Pellino3 augmented the expression of type I interferon but not of proinflammatory cytokines in response to TLR3 activation. Pellino3-deficient mice had greater resistance against the pathogenic and lethal effects of encephalomyocarditis virus (EMCV). TLR3 signaling induced Pellino3, which in turn interacted with and ubiquitinated TRAF6. This modification suppressed the ability of TRAF6 to interact with and activate IRF7, resulting in downregulation of type I interferon expression. Our findings highlight a new physiological role for Pellino3 and define a new autoregulatory network for controlling type I interferon expression.

    Item Type: Article
    Keywords: Gene regulation in immune cells; Signal transduction; Toll-like receptors;
    Academic Unit: Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Faculty of Science and Engineering > Biology
    Item ID: 7111
    Identification Number: https://doi.org/10.1038/ni.2429
    Depositing User: Bernard Mahon
    Date Deposited: 19 May 2016 10:00
    Journal or Publication Title: Nature Immunology
    Publisher: Nature Publishing Group
    Refereed: Yes
    URI:

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