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Survival and maintenance of regulatory T cells require the kinase TAK1

Cellular & Molecular Immunology volume 12, pages 572–579 (2015)Cite this article

Abstract

Regulatory T (Treg) cells play a central role in regulating peripheral immune tolerance and preventing autoimmunity. Despite the extensive studies on the development of Treg cells, the molecular mechanisms that maintain the population of committed Treg cells remain poorly understood. We show here that Treg-conditional ablation of the kinase TAK1 reduced the number of Treg cells in the peripheral lymphoid organs, causing abnormal activation of conventional T cells and autoimmune symptoms. Using an inducible gene knockout approach, we further demonstrate that TAK1 is crucial for the survival of Treg cells. Expression of a constitutively active IκB kinase partially restored the level of Treg cells in the TAK1Treg-KO mice. These results suggest a crucial role for TAK1 for maintaining the survival of committed Treg cells under physiological conditions.

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Acknowledgements

We thank S Akira for TAK1-flox mice. We also thank the personnel from the NIH/NCI-supported resources (flow cytometry, DNA analysis, histology, and animal facilities) under award number P30CA016672 at the MD Anderson Cancer Center. This work was supported by the 2013 Yeungnam University Research Grant, and the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2014S1A2A2027903) to Jae-Hoon Chang and National Institutes of Health grants (AI057555, AI064639, GM84459, and AI104519) to Shao-Cong Sun.

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Authors and Affiliations

  1. Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, 77030, TX, USA

    Jae-Hoon Chang, Hongbo Hu & Shao-Cong Sun

  2. Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, 77030, TX, USA

    Shao-Cong Sun

  3. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, 77030, TX, USA

    Shao-Cong Sun

  4. College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Republic of Korea

    Jae-Hoon Chang

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  1. Jae-Hoon Chang
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Correspondence to Shao-Cong Sun.

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Chang, JH., Hu, H. & Sun, SC. Survival and maintenance of regulatory T cells require the kinase TAK1. Cell Mol Immunol 12, 572–579 (2015). https://doi.org/10.1038/cmi.2015.27

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