Control of Regulatory T Cell Development by the Transcription Factor Foxp3

@article{Hori2003ControlOR,
  title={Control of Regulatory T Cell Development by the Transcription Factor Foxp3},
  author={Shohei Hori and Takashi Nomura and Shimon Sakaguchi},
  journal={Science},
  year={2003},
  volume={299},
  pages={1057 - 1061}
}
Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naïve T… 
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This article proposes that differences in responses between regulatory T cells and effector T cells respond differently to T-cell receptor stimulation are mediated by FOXP3, and are manifested by alterations in biochemical signalling pathways, patterns of gene expression and the appearance of cell-surface homing receptors.

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Recent advances in understanding of the Foxp3-dependent molecular and functional program and the role ofFoxp3 in regulatory T cell biology are reviewed.

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Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo

Analysis of the T cell receptor repertoire suggested that exFoxp3 cells developed from both natural and adaptive Treg cells, suggesting the generation of potentially autoreactive effector T cells as a consequence of Foxp3 instability has important implications for understanding autoimmune disease pathogenesis.

FoxP3 and Regulatory T Cells

In Foxp3-expressing T cell hybridomas,Foxp3 binding to DNA does not lead to the activation or suppression of genes which becomes only visible after T cell activation, in line with observations by others that Foxp 3 exerts important functions through association with T cell receptor-dependent transcription factors in a DNA-binding complex.
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