title: Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions.
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.
authors: Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
authors: Mark
authors: M
authors: Mellett
authors: Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
authors: Paola
authors: P
authors: Atzei
authors: Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
authors: Ronan
authors: R
authors: Bergin
authors: Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland.
authors: Alan
authors: A
authors: Horgan
authors: Helmholtz Zentrum München, Institute of Developmental Genetics, Munich, Neuherberg 85764, Germany.
authors: Thomas
authors: T
authors: Floss
authors: Helmholtz Zentrum München, Institute of Developmental Genetics, Munich, Neuherberg 85764, Germany.
authors: Wolfgang
authors: W
authors: Wurst
authors: UCD School of Veterinary Medicine &Conway Institute of Biomolecular &Biomedical Research, UCD, Belfield, Dublin 4, Ireland.
authors: John J
authors: JJ
authors: Callanan
authors: 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.
authors: Paul N
authors: PN
authors: Moynagh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007249:Inflammation; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology*; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C477526:IL17RD protein, human; C508528:Il17rd protein, mouse; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D018123:Receptors, Interleukin; D051193:Toll-Like Receptors