ZCCHC3 modulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2020,（4）
• 页码范围: 251-262
• 页数: 12页
• 语种: 英文
• DOI: 10.1093/jmcb/mjaa004

摘要

Toll-like receptor 3 (TLR3)-mediated signaling is important for host defense against RNA virus.Upon viral RNA stimulation,toll and interleukin-1 receptor domain-containing adaptor inducing IFN-β (TRIF) is recruited to TLR3 and then undergoes oligomerization,which is required for the recruitment of downstream molecules to transmit signals.Here,we identified zinc finger CCHiC-type containing 3 (ZCCHC3) as a positive regulator of TLR3-mediated signaling.Overexpression of ZCCHC3 promoted transcription of downstream antiviral genes stimulated by the synthetic TLR3 ligand poly(I∶C).ZCCHC3-deficiency markedly inhibited TLR3-but not TLR4-mediated induction of type Ⅰ interferons (IFNs) and proinflammatory cytokines.Zcchc3-/-mice were more resistant to poly(I∶C)-but not lipopolysaccharide-induced inflammatory death.Mechanistically,ZCCHC3 promoted recruitment of TRIF to TLR3 after poly(I∶C) stimulation.Our findings reveal that ZCCHC3 plays an important role in TLR3-mediated innate immune response by promoting the recruitment of TRIF to TLR3 after ligand stimulation.