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

Preview

Download (2MB) | Preview

Abstract

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:	https://doi.org/10.1038/ncomms7669
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
URI:	https://www.nature.com
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

Repository Staff Only(login required)

Item control page

Downloads

Origin of downloads