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Regulatory T Cells: the Many Faces of Foxp3

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Abstract

Regulatory T (Treg) cells expressing the transcription factor forkhead box P3 (Foxp3) play a requisite role in the maintenance of immunological homeostasis and prevention of peripheral self-tolerance breakdown. Although Foxp3 by itself is neither necessary nor sufficient to specify many aspects of the Treg cell phenotype, its sustained expression in Treg cells is indispensable for their phenotypic stability, metabolic fitness, and regulatory function. In this review, we summarize recent advances in Treg cell biology, with a particular emphasis on the role of Foxp3 as a transcriptional modulator and metabolic gatekeeper essential to an effective immune regulatory response. We discuss these findings in the context of human inborn errors of immune dysregulation, with a focus on FOXP3 mutations, leading to Treg cell deficiency. We also highlight emerging concepts of therapeutic Treg cell reprogramming to restore tolerance in the settings of immune dysregulatory disorders.

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Acknowledgments

This work was supported by the National Institutes of Health grants 5R01AI085090 (to T.A.C.)

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  1. Division of Immunology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Peter Georgiev, Louis-Marie Charbonnier & Talal A. Chatila

  2. Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA

    Peter Georgiev, Louis-Marie Charbonnier & Talal A. Chatila

  3. Merck & Co., Inc., Kenilworth, NJ, USA

    Peter Georgiev

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Georgiev, P., Charbonnier, LM. & Chatila, T.A. Regulatory T Cells: the Many Faces of Foxp3. J Clin Immunol 39, 623–640 (2019). https://doi.org/10.1007/s10875-019-00684-7

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