| First Author | Yi YS | Year | 2018 |
| Journal | EBioMedicine | Volume | 29 |
| Pages | 78-91 | PubMed ID | 29472103 |
| Mgi Jnum | J:270123 | Mgi Id | MGI:6276519 |
| Doi | 10.1016/j.ebiom.2018.02.012 | Citation | Yi YS, et al. (2018) p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice. EBioMedicine 29:78-91 |
| abstractText | 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-beta and pro-inflammatory cytokines. The serum levels of IFN-beta 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-kB 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. |
