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  • Review Article
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Foxp3 in control of the regulatory T cell lineage

Abstract

Foxp3, an X chromosome–encoded forkhead transcription factor family member, is indispensable for the differentiation of regulatory T cells. These cells have a vital role in preventing autoimmunity and pathology inflicted by uncontrolled immune responses to infections. Deficiency or mutation in Foxp3 in humans and mice leads to an early onset, highly aggressive and fatal autoimmune disease affecting various tissues. Here, we review recent advances in our understanding of the Foxp3-dependent molecular and functional program and the role of Foxp3 in regulatory T cell biology.

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Figure 1: Foxp3 induction in thymic precursor cells is facilitated by high-affinity TCR engagement combined with additional signals sent through CD28 and common γ chain–containing cytokine receptors (γcR).

Kim Caesar

Figure 2: Foxp3 facilitates Treg cell lineage commitment by amplifying and stabilizing its own expression and by repressing alternative cell fates.

Kim Caesar

Figure 3: The interaction between NFAT and Foxp3 is important for Treg cell differentiation and suppressor function.

Kim Caesar

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Acknowledgements

We are grateful to all members of the Rudensky laboratory for discussions. This work was supported by a Cancer Research Institute postdoctoral fellowship (Y.Z.) and grants from the US National Institutes of Health (A.Y.R.). A.Y.R. is a Howard Hughes Medical Institute Investigator.

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Correspondence to Alexander Y Rudensky.

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Zheng, Y., Rudensky, A. Foxp3 in control of the regulatory T cell lineage. Nat Immunol 8, 457–462 (2007). https://doi.org/10.1038/ni1455

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