Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 11, Pages 6648-6652Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803320
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- National Institutes of Health
- Cancer Research Institute
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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. The Journal of Immunology, 2009, 182: 6648-6652.
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