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    Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia


    Mellett, Mark and Atzei, Paola and Horgan, Alan and Hams, Emily and Floss, Thomas and Wurst, Wolfgang and Fallon, Padraic G. and Moynagh, Paul N. (2012) Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia. Nature Communications, 3 (1119). ISSN 2041-1723

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    Abstract

    Interleukin-17A, the prototypical member of the interleukin-17 cytokine family, coordinates local tissue inflammation by recruiting neutrophils to sites of infection. Dysregulation of interleukin-17 signalling has been linked to the pathogenesis of inflammatory diseases and autoimmunity. The interleukin-17 receptor family members (A–E) have a broad range of functional effects in immune signalling yet no known role has been described for the remaining orphan receptor, interleukin-17 receptor D, in regulating interleukin-17A-induced signalling pathways. Here we demonstrate that interleukin-17 receptor D can differentially regulate the various pathways employed by interleukin-17A. Neutrophil recruitment, in response to in vivo administration of interleukin-17A, is abolished in interleukin-17 receptor D-deficient mice, correlating with reduced interleukin-17A-induced activation of p38 mitogen-activated protein kinase and expression of the neutrophil chemokine MIP-2. In contrast, interleukin-17 receptor D deficiency results in enhanced interleukin-17A-induced activation of nuclear factor-kappa B and interleukin-6 and keratinocyte chemoattractant expression. Interleukin-17 receptor D disrupts the interaction of Act1 and TRAF6 causing differential regulation of nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling pathways.

    Item Type: Article
    Keywords: Orphan receptor; IL-17RD tunes; IL-17A signalling; neutrophilia;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 8127
    Identification Number: https://doi.org/10.1038/ncomms2127
    Depositing User: Professor Paul Moynagh
    Date Deposited: 05 Apr 2017 16:30
    Journal or Publication Title: Nature Communications
    Publisher: Nature Publshing Group
    Refereed: Yes
    URI:

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