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- W75539191 abstract "Abstract Although T-bet and STAT4 are required for Th1 programming, detailed transcriptional networks in Th1 cells have not been clearly defined. Twist1 is a basic helix-loop-helix (bHLH) transcription factor that is regulated by STAT4 in Th1 cells. We demonstrated that knocking down Twist1 in Th1 cells using Twist1-targeting small hairpin RNA vector increased IFN-γ and TNF-α and that overexpression of Twist1 in Th1 cells results in the decrease in IFN-γ and TNF-α production, which correlates with a reduction of STAT4 activation, and the expression of number of Th1 genes including T-bet, Runx3, and Hlx1. However, ectopic expression of Runx3 but not IL-12Rβ2 or T-bet can rescue the inhibitory effect of Twist1. Twist1 functions through several mechanisms including the direct binding of Twist1 to the E-box containing regions of the Ifng, Il12rb2, Tbx21 and Runx3 promoters in activated Th1 cells. Moreover, there is a physical interaction between Twist1 and Runx3 in both cell line and primary T cell culture. This study provides new insight on how Twist1 negatively regulates the Th1 transcriptional network, and how modulating Twist1 expression could be an approach for gene-based therapy in autoimmune diseases mediated by Th1 cells." @default.
- W75539191 created "2016-06-24" @default.
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- W75539191 date "2011-04-01" @default.
- W75539191 modified "2023-09-24" @default.
- W75539191 title "Twist1 regulates Th1 cell development by interfering with its transcriptional network (113.11)" @default.
- W75539191 doi "https://doi.org/10.4049/jimmunol.186.supp.113.11" @default.
- W75539191 hasPublicationYear "2011" @default.
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