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IL-7 signalling represses Bcl-6 and the TFH gene program

Author

Listed:
  • Paul W. McDonald

    (Virginia Tech Carilion Research Institute)

  • Kaitlin A. Read

    (Virginia Tech Carilion Research Institute)

  • Chandra E. Baker

    (Virginia Tech Carilion Research Institute)

  • Ashlyn E. Anderson

    (Virginia Tech Carilion Research Institute)

  • Michael D. Powell

    (Virginia Tech Carilion Research Institute)

  • André Ballesteros-Tato

    (University of Alabama at Birmingham, Birmingham, Alabama 35294, USA)

  • Kenneth J. Oestreich

    (Virginia Tech Carilion Research Institute
    Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech
    Virginia Tech Carilion School of Medicine)

Abstract

The transcriptional repressor Bcl-6 is linked to the development of both CD4+ T follicular helper (TFH) and central memory T (TCM) cells. Here, we demonstrate that in response to decreased IL-2 signalling, T helper 1 (TH1) cells upregulate Bcl-6 and co-initiate TFH- and TCM-like gene programs, including expression of the cytokine receptors IL-6Rα and IL-7R. Exposure of this potentially bi-potent cell population to IL-6 favours the TFH gene program, whereas IL-7 signalling represses TFH-associated genes including Bcl6 and Cxcr5, but not the TCM-related genes Klf2 and Sell. Mechanistically, IL-7-dependent activation of STAT5 contributes to Bcl-6 repression. Importantly, antigen-specific IL-6Rα+IL-7R+ CD4+ T cells emerge from the effector population at late time points post influenza infection. These data support a novel role for IL-7 in the repression of the TFH gene program and evoke a divergent regulatory mechanism by which post-effector TH1 cells may contribute to long-term cell-mediated and humoral immunity.

Suggested Citation

  • Paul W. McDonald & Kaitlin A. Read & Chandra E. Baker & Ashlyn E. Anderson & Michael D. Powell & André Ballesteros-Tato & Kenneth J. Oestreich, 2016. "IL-7 signalling represses Bcl-6 and the TFH gene program," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10285
    DOI: 10.1038/ncomms10285
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    Cited by:

    1. Kaitlin A. Read & Devin M. Jones & Srijana Pokhrel & Emily D. S. Hales & Aditi Varkey & Jasmine A. Tuazon & Caprice D. Eisele & Omar Abdouni & Abbey Saadey & Melissa R. Leonard & Robert T. Warren & Mi, 2023. "Aiolos represses CD4+ T cell cytotoxic programming via reciprocal regulation of TFH transcription factors and IL-2 sensitivity," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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