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Access through your institution Buy or subscribe As germline-encoded pattern recognition receptors, Toll-like receptors (TLRs) play important roles in innate immune responses against various
pathogens.1 Among TLR family members, only TLR3 and TLR4 use TIR domain-containing adapter-inducing interferon-β (TRIF) as an adapter protein to trigger the production of type I interferon
(IFN-Ι) and inflammatory cytokines.1,2 Secreted IFNs then bind their plasma membrane receptors, further stimulating the transcription of IFN-stimulated genes (ISGs), which have multiple
antiviral functions, such as restricting the replication and assembly of viral particles.3 We previously reported an accessory protein, named WD repeat and FYVE domain-containing protein
(WDFY1), that strengths the interaction between TRIF and TLR3 or TLR4.4 At the cellular level, overexpression of WDFY1 reinforced TLR3/4-mediated innate immune responses, and the suppression
of WDFY1 by RNAi had the opposite effects. We also reported that the function of WDFY1 is highly dependent on its FYVE domain, which is responsible for its localization to the early
endosome.5 However, whether Wdfy1-knockout (KO) mice are susceptible to Tlr3 or Tlr4 ligands remains unknown. We then performed similar experiments using mouse embryonic fibroblasts (MEFs).
Knockout of Wdfy1 markedly impaired poly I:C-induced transcription of _Ifnb1_, _Isg56_, _Tnfa_, _Il6_, and _Il1b_ (Fig. 1b). However, in LPS-treated MEFs, knockout of Wdfy1 impaired the
transcription of _Ifnb1_ but had no marked effect on the transcription of _Isg56_, _Tnfa_, _Il6_, or _Il1b_ (Supplementary information, Fig. S1b). These results suggest that in nonimmune
cells, Wdfy1 mainly participates in Tlr3 signaling and Tlr4-mediated production of Ifn-I but not Tlr4-mediated production of inflammatory cytokines. This is a preview of subscription
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subscriptions * Read our FAQs * Contact customer support REFERENCES * Fitzgerald, K. A. & Kagan, J. C. Toll-like receptors and the control of immunity. _Cell_ 180, 1044–1066 (2020).
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allergic rhinitis pathogenesis. _Allergologia et. Immunopathologia_ 46, 503–507 (2018). Article CAS Google Scholar Download references ACKNOWLEDGEMENTS This work was supported by the
National Key Research and Development Program of China (2018YFA0800700) and the National Natural Science Foundation of China (31970894, 31770941). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS
* State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan, 430072, China Yang Yang & Yu Liu * State
Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, 430062, China Yun-Hong Hu Authors * Yang Yang View author publications You can also
search for this author inPubMed Google Scholar * Yun-Hong Hu View author publications You can also search for this author inPubMed Google Scholar * Yu Liu View author publications You can
also search for this author inPubMed Google Scholar CONTRIBUTIONS Y.Y. and Y.H.H. performed the experiments and analyzed the data, L.Y. designed the research and wrote the paper.
CORRESPONDING AUTHOR Correspondence to Yu Liu. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare that they have no conflicts of interest. SUPPLEMENTARY INFORMATION SUPPLEMENTARY
FIGURE S1 SUPPLEMENTARY FIGURE LEGEND RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yang, Y., Hu, YH. & Liu, Y. Wdfy1 deficiency impairs
Tlr3-mediated immune responses in vivo. _Cell Mol Immunol_ 17, 1014–1016 (2020). https://doi.org/10.1038/s41423-020-0461-4 Download citation * Received: 30 March 2020 * Accepted: 22 April
2020 * Published: 12 May 2020 * Issue Date: September 2020 * DOI: https://doi.org/10.1038/s41423-020-0461-4 SHARE THIS ARTICLE Anyone you share the following link with will be able to read
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