Document Detail


Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia.
MedLine Citation:
PMID:  23047677     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Interleukin-17A, the prototypical member of the interleukin-17 cytokine family, coordinates local tissue inflammation by recruiting neutrophils to sites of infection. Dysregulation of interleukin-17 signalling has been linked to the pathogenesis of inflammatory diseases and autoimmunity. The interleukin-17 receptor family members (A-E) have a broad range of functional effects in immune signalling yet no known role has been described for the remaining orphan receptor, interleukin-17 receptor D, in regulating interleukin-17A-induced signalling pathways. Here we demonstrate that interleukin-17 receptor D can differentially regulate the various pathways employed by interleukin-17A. Neutrophil recruitment, in response to in vivo administration of interleukin-17A, is abolished in interleukin-17 receptor D-deficient mice, correlating with reduced interleukin-17A-induced activation of p38 mitogen-activated protein kinase and expression of the neutrophil chemokine MIP-2. In contrast, interleukin-17 receptor D deficiency results in enhanced interleukin-17A-induced activation of nuclear factor-kappa B and interleukin-6 and keratinocyte chemoattractant expression. Interleukin-17 receptor D disrupts the interaction of Act1 and TRAF6 causing differential regulation of nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling pathways.
Authors:
Mark Mellett; Paola Atzei; Alan Horgan; Emily Hams; Thomas Floss; Wolfgang Wurst; Padraic G Fallon; Paul N Moynagh
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature communications     Volume:  3     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1119     Citation Subset:  IM    
Affiliation:
Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, Ireland.
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