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Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage?

Abstract

Regulatory T (TReg) cells constitute a unique T-cell lineage that has a crucial role in immunological tolerance. Several years ago, forkhead box P3 (FOXP3) was identified as the transcription factor that was responsible for determining the development and function of these cells. However, the underlying mechanisms that are involved in the regulation of the FOXP3 gene remain unclear and therefore preclude accurate identification and manipulation of TReg cells. In this Progress article, we summarize recent advances in understanding how FOXP3 expression is controlled and highlight evidence suggesting that epigenetic regulation of the FOXP3 locus contributes to its role as a lineage-specification factor.

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Figure 1: The origin of regulatory T cells in the thymus and the periphery.
Figure 2: Multiple signalling pathways converge for the induction of forkhead box P3 expression.
Figure 3: The FOXP3 locus is subject to epigenetic control.

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Acknowledgements

We thank A. Rao for helpful discussions and R. Baumgrass, B. Schraven, J. Lindquist and M. Merkenschlager for critical reading of the manuscript.

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Huehn, J., Polansky, J. & Hamann, A. Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage?. Nat Rev Immunol 9, 83–89 (2009). https://doi.org/10.1038/nri2474

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