Cutting edge: TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1 Journal Article
| Authors: | Josefowicz, S. Z.; Wilson, C. B.; Rudensky, A. Y. |
| Article Title: | Cutting edge: TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1 |
| 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-β was dispensable for Foxp3 expression. In addition, CD4-Cre x dnmt1<sup>fl/fl</sup> mice harbored sizeable thymic and peripheral populations of CD8<sup>+</sup> Foxp3<sup>+</sup> 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-β facilitates Foxp3 induction in part by opposing cell cycle-dependent Dnmt1 recruitment, leading to locus inactivation. Copyright © 2009 by The American Association of Immunologists, Inc. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; genetics; nonhuman; cd8+ t lymphocyte; t lymphocyte; cd8-positive t-lymphocytes; forkhead transcription factors; animal cell; mouse; animal; metabolism; mouse mutant; animals; mice; mice, knockout; transforming growth factor beta; transcription initiation; physiology; t lymphocyte receptor; immunology; thymus; receptors, antigen, t-cell; cd4+ t lymphocyte; cd4-positive t-lymphocytes; transforming growth factor beta1; cd4 antigen; forkhead transcription factor; transcriptional activation; lymphocyte antigen receptor; lymphocyte count; dna methyltransferase 1; forkhead transcription factor 3; dna (cytosine 5 ) methyltransferase 1; dna (cytosine 5) methyltransferase; dna (cytosine-5-)-methyltransferase 1; foxp3 protein, mouse; dna (cytosine-5-)-methyltransferase |
| Journal Title: | Journal of Immunology |
| Volume: | 182 |
| Issue: | 11 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2009-06-01 |
| Start Page: | 6648 |
| End Page: | 6652 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0803320 |
| PUBMED: | 19454658 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 14" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus" |
