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YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity

Author

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  • Soo Seok Hwang

    (Sogang University
    Yale University School of Medicine
    Howard Hughes Medical Institute, Yale School of Medicine)

  • Sung Woong Jang

    (Sogang University)

  • Min Kyung Kim

    (Sogang University)

  • Lark Kyun Kim

    (Yale University School of Medicine
    Howard Hughes Medical Institute, Yale School of Medicine)

  • Bong-Sung Kim

    (Yale University School of Medicine
    Hand Surgery—Burn Center, Medical Faculty, RWTH Aachen University
    Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University)

  • Hyeong Su Kim

    (Sogang University)

  • Kiwan Kim

    (Sogang University)

  • Wonyong Lee

    (Sogang University)

  • Richard A. Flavell

    (Yale University School of Medicine
    Howard Hughes Medical Institute, Yale School of Medicine)

  • Gap Ryol Lee

    (Sogang University)

Abstract

Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for Treg-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in Treg cells than Tconv cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in Treg cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of Treg cells by blocking Foxp3.

Suggested Citation

  • Soo Seok Hwang & Sung Woong Jang & Min Kyung Kim & Lark Kyun Kim & Bong-Sung Kim & Hyeong Su Kim & Kiwan Kim & Wonyong Lee & Richard A. Flavell & Gap Ryol Lee, 2016. "YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity," Nature Communications, Nature, vol. 7(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10789
    DOI: 10.1038/ncomms10789
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