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- W188689013 abstract "Abstract Foxp3 expression is regulated by multiple cytokine signals. While TGFβ and IL-2 are required for the induction and the maintenance of Foxp3 expression, others such as IL-4, IL-6 and IL-27 have been reported to inhibit Foxp3 induction. Despite the previous reports that demonstrated the indispensable role of the Stat3 signaling pathway for IL-6 and IL-27 mediated inhibition of Foxp3 expression, we have found that Stat3 was dispensable for the IL-27 mediated Foxp3 inhibition. Interestingly, while the IL-6 mediated inhibition was effectively reversed by retinoic acid (RA) in Stat3-/- T cells stimulated in the presence of TGFβ, RA failed to reverse IL-27 mediated Foxp3 inhibition. During Foxp3 induction, IL-27 significantly counteracted TGFβ-mediated acetylation of chromosomal histones in the Foxp3 regulatory elements, which was reversed by the addition of DNA methyltransferase inhibitor RG108. In addition to the increased expression of Dnmt1 and Dnmt3a, IL-27 potently enhanced the recruitment of at least Dnmt1 to the Foxp3 loci. Finally, the addition of inhibitors of DNA methyltransferase and histone deacetylases reversed the inhibitory effect by IL-27. These data indicate that IL-27 enhances DNA methylation and subsequent histone deacetylation in the Foxp3 loci, which results in silencing of Foxp3 gene expression. In addition, IL-27 may inhibit Foxp3 expression via a different mechanism from those mediated by IL-6." @default.
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- W188689013 date "2011-04-01" @default.
- W188689013 modified "2023-10-16" @default.
- W188689013 title "IL-27 mediated silencing of Foxp3 gene expression via enhanced DNA methylation (152.26)" @default.
- W188689013 doi "https://doi.org/10.4049/jimmunol.186.supp.152.26" @default.
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