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Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis

Author

Listed:
  • Sonja Reißig

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Yilang Tang

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Alexei Nikolaev

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Katharina Gerlach

    (University Erlangen-Nürnberg)

  • Christine Wolf

    (Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD))

  • Kathrin Davari

    (Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD))

  • Christian Gallus

    (Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD))

  • Joumana Masri

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Ilgiz A. Mufazalov

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Markus F. Neurath

    (University Erlangen-Nürnberg)

  • F. Thomas Wunderlich

    (Max Planck Institute for Metabolism Research, CECAD, CMMC, Institute for Genetics)

  • Jörn M. Schattenberg

    (University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Peter R. Galle

    (University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Benno Weigmann

    (University Erlangen-Nürnberg)

  • Ari Waisman

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz)

  • Elke Glasmacher

    (Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD))

  • Nadine Hövelmeyer

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz)

Abstract

Bcl-3 is an atypical NF-κB family member that regulates NF-κB-dependent gene expression in effector T cells, but a cell-intrinsic function in regulatory T (Treg) cells and colitis is not clear. Here we show that Bcl-3 expression levels in colonic T cells correlate with disease manifestation in patients with inflammatory bowel disease. Mice with T-cell-specific overexpression of Bcl-3 develop severe colitis that can be attributed to defective Treg cell development and function, leading to the infiltration of immune cells such as pro-inflammatory γδT cells, but not αβ T cells. In Treg cells, Bcl-3 associates directly with NF-κB p50 to inhibit DNA binding of p50/p50 and p50/p65 NF-κB dimers, thereby regulating NF-κB-mediated gene expression. This study thus reveals intrinsic functions of Bcl-3 in Treg cells, identifies Bcl-3 as a potential prognostic marker for colitis and illustrates the mechanism by which Bcl-3 regulates NF-κB activity in Tregs to prevent colitis.

Suggested Citation

  • Sonja Reißig & Yilang Tang & Alexei Nikolaev & Katharina Gerlach & Christine Wolf & Kathrin Davari & Christian Gallus & Joumana Masri & Ilgiz A. Mufazalov & Markus F. Neurath & F. Thomas Wunderlich & , 2017. "Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15069
    DOI: 10.1038/ncomms15069
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