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- W4313374496 abstract "Abstract Cytokines are key factors for initiating inflammatory response and among them IFN-I is one of the most versatile because of its dual roles in antiviral and inflammatory activities. While STAT1 and STAT2 are critical for triggering antiviral response, the signaling events downstream of IFN-I receptor contributing to inflammation have yet to be defined. Here we demonstrate that STAT3 and one of its interacting partners PLSCR2 negatively regulate IFN-I-mediated antiviral and inflammatory response. Enhanced expression of IFN-I-stimulated genes (ISGs) is found in cells either absence of STAT3 or PLSCR2, leading to increased resistance to viral infection in vitro and in vivo. Moreover, STAT3 can cooperate with PLSCR2 to suppress IFN-I response. Interestingly, GSEA analysis for IFN-I-stimulated cells lacking PLSCR2 versus WT control displays an inflammatory signature with increased expression of inflammatory cytokines and chemokines, their receptors and TLRs. Stimulation of TLR ligands, including LPS, R848 or CpG, also results in enhanced expression of IFN-I and inflammatory cytokines and chemokines in PLSCR2KO cells as opposed to WT control. PLSCR2KO mice are also more susceptible to LPS-induced endotoxic shock in vivo with increased serum TFN. Similarly, PLSCR2KO mice also display increased acute lung injury in response to intratracheal administration of LPS with increased infiltration of macrophages and neutrophils and production of inflammatory cytokines and chemokines. Enhanced TLR response is also found in STAT3KO BM-derived macrophages. Therefore, these results demonstrate that STAT3 coordinates with PLSCR2 to regulate antiviral and inflammatory response and define a novel axis in modulating IFN-I-mediated response." @default.
- W4313374496 created "2023-01-06" @default.
- W4313374496 creator A5067335835 @default.
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- W4313374496 date "2020-05-01" @default.
- W4313374496 modified "2023-09-27" @default.
- W4313374496 title "Regulatory Role of STAT3-PLSCR2 Axis in Antiviral and Inflammatory Response" @default.
- W4313374496 doi "https://doi.org/10.4049/jimmunol.204.supp.79.18" @default.
- W4313374496 hasPublicationYear "2020" @default.
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