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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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
JournalNature Communications
StatePublished - Mar 2015
Externally publishedYes


Dive into the research topics of 'Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions'. Together they form a unique fingerprint.

Cite this