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Foxp3+ regulatory T cells: differentiation, specification, subphenotypes

Abstract

Regulatory T cells (Treg cells) characterized by expression of the transcription factor Foxp3 play a key role in immune homeostasis. Rather than a monomorphic population strictly determined by Foxp3 as a 'master regulator', the emerging view is one of Treg cells as a population with many levels of complexity. Several regulatory factors partake in the control of their transcriptional 'signature', with Foxp3 being a key regulator but insufficient and unnecessary to specify all aspects of the lineage. Distinct subphenotypes of Foxp3+ Treg cells are found in different anatomical locations. Some subphenotypes specifically control different facets of effector T cell function and, perhaps surprisingly, share transcriptional control elements with the very cells they regulate. This review will focus on these novel aspects of Treg cell diversity.

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Figure 1: Treg cell signature genes and their cellular localization.
Figure 2: Differential signaling induces or inhibits Treg cell differentiation.
Figure 3: Different segments of the Treg signature appear in different contexts.

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Acknowledgements

We thank J. Powell, R. Flavell, D. Campbell, J. Lafaille, R. Maizels, V. Kuchroo and A. Rudensky for discussions and communication of unpublished data. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R01-AI051530), the Juvenile Diabetes Research Foundation (4-2007-1057), the German Research Foundation (Emmy-Noether Fellowship FE 801/1-1 to M.F.), the Charles A. King Fund (M.F.) and the Canadian Institutes of Health Research (J.H.).

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Feuerer, M., Hill, J., Mathis, D. et al. Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat Immunol 10, 689–695 (2009). https://doi.org/10.1038/ni.1760

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