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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Mellett M,Atzei P,Bergin R,Horgan A,Floss T,Wurst W,Callanan JJ,Moynagh PNdoi
10.1038/ncomms7669subject
Has Abstractpub_date
2015-03-26 00:00:00pages
6669issn
2041-1723pii
ncomms7669journal_volume
6pub_type
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