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    Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions

    Mellett, Mark and Atzei, Paola and Bergin, Ronan and Horgan, Alan and Floss, Thomas and Wurst, Wolfgang and Callanan, John J. and Moynagh, Paul N. (2015) Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions. Nature Communications, 6 (6669). ISSN 2041-1723

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    Receptor families of the innate immune response engage in ‘cross-talk’ to tailor optimal immune responses against invading pathogens. However, these responses are subject to multiple levels of regulation to keep in check aberrant inflammatory signals. Here, we describe a role for the orphan receptor interleukin-17 receptor D (IL-17RD) in negatively regulating Toll-like receptor (TLR)-induced responses. Deficiency of IL-17RD expression in cells leads to enhanced pro-inflammatory signalling and gene expression in response to TLR stimulation, and Il17rd−/− mice are more susceptible to TLR-induced septic shock. We demonstrate that the intracellular Sef/IL-17R (SEFIR) domain of IL-17RD targets TIR adaptor proteins to inhibit TLR downstream signalling thus revealing a paradigm involving cross-regulation of members of the IL-17R and TLR families.

    Item Type: Article
    Keywords: Cell signalling; Interleukins; Regulatory networks; Toll-like receptors;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 11036
    Identification Number:
    Depositing User: Professor Paul Moynagh
    Date Deposited: 16 Sep 2019 13:55
    Journal or Publication Title: Nature Communications
    Publisher: Nature Publshing Group
    Refereed: Yes
    Funders: Immunology Research Centre, Science Foundation Ireland (SFI), Programme for Research in Third Level Institutions (PRTLI) Cycle 5
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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