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  • Title: Cutting edge: TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1.
    Author: Josefowicz SZ, Wilson CB, Rudensky AY.
    Journal: J Immunol; 2009 Jun 01; 182(11):6648-52. PubMed ID: 19454658.
    Abstract:
    TCR signaling is important for regulatory T cell (Tr) development. Using a genetic model of DNA methyltransferase 1 (Dnmt1) deficiency, we observed highly efficient Foxp3 induction following TCR stimulation, suggesting a dominant role for TCR signaling in Foxp3 induction. In the absence of Dnmt1, Foxp3 induction in thymic and peripheral Foxp3-negative T cells was maximized upon TCR engagement, and the provision of TGF-beta was dispensable for Foxp3 expression. In addition, CD4-Cre x dnmt1(fl/fl) mice harbored sizeable thymic and peripheral populations of CD8(+)Foxp3(+) cells, suggesting that Dnmt1 activity is required for restricting Foxp3 expression to the CD4 T cell lineage. Our results suggest that the TCR signal is sufficient for transcriptional activation of Foxp3 in the absence of maintenance DNA methylation and that TGF-beta facilitates Foxp3 induction in part by opposing cell cycle-dependent Dnmt1 recruitment, leading to locus inactivation.
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