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Transcriptional modulation of regulatory T cell development by novel regulators NR4As

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Abstract

Regulatory T (Treg) cells with high expression of both CD25 and Foxp3 are developed in the thymus and also peripheral tissues. Treg cells suppress the activation and functions of effector T cells raised against specific antigens and are crucial for maintaining immune homeostasis. Treg cell development is associated with the induction of and epigenetic alterations of forkhead transcription factor Foxp3. Foxp3 expression is increased by the activation of several transcription factors including nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and Smad3 in response to various signals such as TGFβ, retinoic acid, and rapamycin. Recently, the orphan nuclear receptor 4A proteins (NR4As) including NR4A1 (Nur77), NR4A2 (Nurr1), and NR4A3 (Nor1) are reported to regulate Treg cell development through activation of Foxp3 and have therapeutic potentials in treating immune disorders. This review summarizes the function and regulatory mechanisms of Treg cells and also implicates current advances in immunomodulatory functions of NR4As and their therapeutic potentials in inflammation and cancer.

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Acknowledgments

This work was supported by Mid-career Researcher Program (2013R1A2A2A01068302 for ESH and 2015R1D1A1A01056936 for HYW) through NRF grant funded by the MEST.

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  1. College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Korea

    Hee Yeon Won & Eun Sook Hwang

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Won, H.Y., Hwang, E.S. Transcriptional modulation of regulatory T cell development by novel regulators NR4As. Arch. Pharm. Res. 39, 1530–1536 (2016). https://doi.org/10.1007/s12272-016-0803-z

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