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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Mellett M,Atzei P,Bergin R,Horgan A,Floss T,Wurst W,Callanan JJ,Moynagh PN

doi

10.1038/ncomms7669

subject

Has Abstract

pub_date

2015-03-26 00:00:00

pages

6669

issn

2041-1723

pii

ncomms7669

journal_volume

6

pub_type

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