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

Mark Mellett, Paola Atzei, Ronan Bergin, Alan Horgan, Thomas Floss, Wolfgang Wurst, John J Callanan, Paul N Moynagh

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17 Citations (Scopus)

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.

Original languageEnglish
Article number6669
Number of pages15
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 26 Mar 2015

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    Mellett, M., Atzei, P., Bergin, R., Horgan, A., Floss, T., Wurst, W., Callanan, J. J., & Moynagh, P. N. (2015). Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions. Nature Communications, 6, [6669]. https://doi.org/10.1038/ncomms7669