Journal
EMBO REPORTS
Volume 16, Issue 4, Pages 447-455Publisher
WILEY-BLACKWELL
DOI: 10.15252/embr.201439637
Keywords
signal transduction; TLR; TRIF; WDFY1
Categories
Funding
- Ministry of Science and Technology of China [2014CB910103, 2012CB910201]
- National Natural Science Foundation of China [31370867, 31221061, 31130020, 91029302]
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Toll-like receptors (TLRs) are pattern recognition receptors that sense a variety of pathogens, initiate innate immune responses, and direct adaptive immunity. All TLRs except TLR3 recruit the adaptor MyD88 to ultimately elicit inflammatory gene expression, whereas TLR3 and internalized TLR4 use TIR-domain-containing adaptor TRIF for the induction of type I interferon and inflammatory cytokines. Here, we identify the WD repeat and FYVE-domain-containing protein WDFY1 as a crucial adaptor protein in the TLR3/4 signaling pathway. Overexpression of WDFY1 potentiates TLR3-and TLR4-mediated activation of NF-kappa B, interferon regulatory factor 3 (IRF3), and production of type I interferons and inflammatory cytokines. WDFY1 depletion has the opposite effect. WDFY1 interacts with TLR3 and TLR4 and mediates the recruitment of TRIF to these receptors. Our findings suggest a crucial role for WDFY1 in bridging the TLR-TRIF interaction, which is necessary for TLR signaling.
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