Peer-Reviewed Journal Details
Mandatory Fields
Mellett, M;Atzei, P;Bergin, R;Horgan, A;Floss, T;Wurst, W;Callanan, JJ;Moynagh, PN
2015
March
Nature Communications
Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions
Published
28 ()
Optional Fields
NF-KAPPA-B DOMAIN-CONTAINING ADAPTER CUTTING EDGE DROSOPHILA TOLL ACTIVATION PATHWAY SEF PROTEIN KINASE FAMILY
6
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.
LONDON
2041-1723
10.1038/ncomms7669
Grant Details