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:	Publisher
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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