| First Author | Zang R | Year | 2020 |
| Journal | J Mol Cell Biol | Volume | 12 |
| Issue | 4 | Pages | 251-262 |
| PubMed ID | 32133501 | Mgi Jnum | J:319508 |
| Mgi Id | MGI:6864370 | Doi | 10.1093/jmcb/mjaa004 |
| Citation | Zang R, et al. (2020) ZCCHC3 modulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3. J Mol Cell Biol 12(4):251-262 |
| abstractText | 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-beta (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 CCHC-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. |
