Document Detail


Pellino3 targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons.
MedLine Citation:
PMID:  23042151     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Toll-like receptors (TLRs) sense pathogen-associated molecules and respond by inducing cytokines and type I interferon. Here we show that genetic ablation of the E3 ubiquitin ligase Pellino3 augmented the expression of type I interferon but not of proinflammatory cytokines in response to TLR3 activation. Pellino3-deficient mice had greater resistance against the pathogenic and lethal effects of encephalomyocarditis virus (EMCV). TLR3 signaling induced Pellino3, which in turn interacted with and ubiquitinated TRAF6. This modification suppressed the ability of TRAF6 to interact with and activate IRF7, resulting in downregulation of type I interferon expression. Our findings highlight a new physiological role for Pellino3 and define a new autoregulatory network for controlling type I interferon expression.
Authors:
Jakub Siednienko; Ruaidhri Jackson; Mark Mellett; Nezira Delagic; Shuo Yang; Bingwei Wang; Lisa S Tang; John J Callanan; Bernard P Mahon; Paul N Moynagh
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-07
Journal Detail:
Title:  Nature immunology     Volume:  -     ISSN:  1529-2916     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland. [2].
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