Pellino3 targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons
- Resource Type
- Authors
- Paul N. Moynagh; Shuo Yang; Jakub Siednienko; Nezira Delagic; Bingwei Wang; Ruaidhri Jackson; John J. Callanan; Bernard P. Mahon; Lisa S. Tang; Mark Mellett
- Source
- Nature immunology. 13(11)
- Subject
- Interferon Regulatory Factor-7
Ubiquitin-Protein Ligases
Immunology
Proinflammatory cytokine
Mice
Interferon
medicine
Cardiovirus Infections
Immunology and Allergy
Animals
Homeostasis
Encephalomyocarditis virus
Regulation of gene expression
Mice, Knockout
TNF Receptor-Associated Factor 6
biology
Ubiquitin
Ubiquitination
Ubiquitin ligase
Cell biology
Toll-Like Receptor 3
Survival Rate
Gene Expression Regulation
TLR3
Interferon Type I
biology.protein
IRF7
Signal transduction
Interferon type I
medicine.drug
Signal Transduction
- Language
- ISSN
- 1529-2916
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.