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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / immunology
-
Adaptor Proteins, Signal Transducing / metabolism
-
Animals
-
Cell Line
-
Gene Expression Regulation*
-
Gene Knockdown Techniques
-
HEK293 Cells
-
Humans
-
Immunity, Innate / genetics
-
Immunity, Innate / immunology*
-
Inflammation
-
Interferon Regulatory Factors / genetics
-
Interferon Regulatory Factors / immunology*
-
Mice
-
Mice, Knockout
-
NF-kappa B / immunology*
-
Protein Structure, Tertiary
-
Receptors, Interleukin / genetics
-
Receptors, Interleukin / immunology*
-
Shock, Septic / genetics
-
Shock, Septic / immunology*
-
Signal Transduction
-
Toll-Like Receptors / immunology*
-
Toll-Like Receptors / metabolism
Substances
-
Adaptor Proteins, Signal Transducing
-
IL17RD protein, human
-
Il17rd protein, mouse
-
Interferon Regulatory Factors
-
NF-kappa B
-
Receptors, Interleukin
-
Toll-Like Receptors