| First Author | Josefowicz SZ | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 11 | Pages | 6648-52 |
| PubMed ID | 19454658 | Mgi Jnum | J:148875 |
| Mgi Id | MGI:3847042 | Doi | 10.4049/jimmunol.0803320 |
| Citation | Josefowicz SZ, et al. (2009) Cutting edge: TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1. J Immunol 182(11):6648-52 |
| abstractText | 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. |
