2. Academic Validation
  3. Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions

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

  • Nat Commun. 2015 Mar 26;6:6669. doi: 10.1038/ncomms7669.
Mark Mellett 1,  Paola Atzei 1,  Ronan Bergin 1,  Alan Horgan 1,  Thomas Floss 2,  Wolfgang Wurst 2,  John J Callanan 3,  Paul N Moynagh 4
Affiliations

Affiliations

  • 1 Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
  • 2 Helmholtz Zentrum München, Institute of Developmental Genetics, Munich, Neuherberg 85764, Germany.
  • 3 UCD School of Veterinary Medicine &Conway Institute of Biomolecular &Biomedical Research, UCD, Belfield, Dublin 4, Ireland.
  • 4 1] Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland [2] Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland BT9 7AE, UK.
PMID: 25808990 DOI: 10.1038/ncomms7669
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.

Figures
Products