Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity

Adrian Tun-Kyi, Greg Finn, Alex Greenwood, Michael Nowak, Tae Ho Lee, John M. Asara, George C. Tsokos, Kate Fitzgerald, Elliot Israel, Xiaoxia Li, Mark Exley, Linda K. Nicholson, Kun Ping Lu

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Toll-like receptors (TLRs) shape innate and adaptive immunity to microorganisms. The enzyme IRAK1 transduces signals from TLRs, but mechanisms for its activation and regulation remain unknown. We found here that TLR7 and TLR9 activated the isomerase Pin1, which then bound to IRAK1; this resulted in activation of IRAK1 and facilitated its release from the receptor complex to activate the transcription factor IRF7 and induce type I interferons. Consequently, Pin1-deficient cells and mice failed to mount TLR-mediated, interferon-dependent innate and adaptive immune responses. Given the critical role of aberrant activation of IRAK1 and type I interferons in various immune diseases, controlling IRAK1 activation via inhibition of Pin1 may represent a useful therapeutic approach. © 2011 Nature America, Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)733-741
    Number of pages8
    JournalNature Immunology
    Volume12
    Issue number8
    DOIs
    Publication statusPublished - Aug 2011

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