p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice

Young Su Yi, Jinlong Jian, Elena Gonzalez-Gugel, Yong Xiang Shi, Qingyun Tian, Wenyu Fu, Aubryanna Hettinghouse, Wenhao Song, Ronghan Liu, Michun He, Huabing Qi, Jing Yang, Xiaolan Du, Guo Zhi Xiao, Lin Chen, Chuan ju Liu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


p204, a murine member of an interferon-inducible p200 family, was reported to recognize intracellular viral and bacterial DNAs, however, its role in the innate immunity in vivo remains unknown due to the lack of p204-deficient animal models. In this study we first generated the p204−/− mice. Unexpectedly, p204 deficiency led to significant defect in extracellular LPS signaling in macrophages, as demonstrated by dramatic reductions of LPS-mediated IFN-β and pro-inflammatory cytokines. The serum levels of IFN-β and pro-inflammatory cytokines were also significantly reduced in p204−/− mice following LPS challenge. In addition, p204−/− mice were resistant to LPS-induced shock. LPS-activated NF-ĸB and IRF-3 pathways were all defective in p204-deficient macrophages. p204 binds to TLR4 through its Pyrin domain, and it is required for the dimerization of TLR4 following LPS-challenge. Collectively, p204 is a critical component of canonical LPS-TLR4 signaling pathway, and these studies also suggest that p204 could be a potential target to prevent and treat inflammatory and infectious diseases.

Original languageEnglish
Pages (from-to)78-91
Number of pages14
StatePublished - Mar 2018
Externally publishedYes


  • IFN-β
  • Inflammatory responses
  • LPS
  • Macrophages
  • TLR4
  • p204


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