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Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis

Author

Listed:
  • Tom Sidwell

    (The University of Melbourne
    Walter and Eliza Hall Institute of Medical Research)

  • Yang Liao

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Alexandra L. Garnham

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Ajithkumar Vasanthakumar

    (The University of Melbourne
    Walter and Eliza Hall Institute of Medical Research)

  • Renee Gloury

    (The University of Melbourne
    Walter and Eliza Hall Institute of Medical Research)

  • Jonas Blume

    (The University of Melbourne
    Walter and Eliza Hall Institute of Medical Research)

  • Peggy P. Teh

    (The University of Melbourne
    Walter and Eliza Hall Institute of Medical Research
    Renal Medicine, Alfred Health
    Western Health)

  • David Chisanga

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Christoph Thelemann

    (Walter and Eliza Hall Institute of Medical Research)

  • Fabian Labastida Rivera

    (QIMR Berghofer Medical Research Institute)

  • Christian R. Engwerda

    (QIMR Berghofer Medical Research Institute)

  • Lynn Corcoran

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Kohei Kometani

    (RIKEN Center for Integrative Medical Sciences (IMS))

  • Tomohiro Kurosaki

    (RIKEN Center for Integrative Medical Sciences (IMS)
    Osaka University)

  • Gordon K. Smyth

    (Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Wei Shi

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Axel Kallies

    (The University of Melbourne
    Walter and Eliza Hall Institute of Medical Research)

Abstract

Differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells are strictly controlled by T-cell receptor (TCR) signals; however, molecular mechanisms that govern these processes are incompletely understood. Here we show that Bach2 is an important regulator of Treg cell differentiation and homeostasis downstream of TCR signaling. Bach2 prevents premature differentiation of fully suppressive effector Treg (eTreg) cells, limits IL-10 production and is required for the development of peripherally induced Treg (pTreg) cells in the gastrointestinal tract. Bach2 attenuates TCR signaling-induced IRF4-dependent Treg cell differentiation. Deletion of IRF4 promotes inducible Treg cell differentiation and rescues pTreg cell differentiation in the absence of Bach2. In turn, loss of Bach2 normalizes eTreg cell differentiation of IRF4-deficient Treg cells. Mechanistically, Bach2 counteracts the DNA-binding activity of IRF4 and limits chromatin accessibility, thereby attenuating IRF4-dependent transcription. Thus, Bach2 balances TCR signaling induced transcriptional activity of IRF4 to maintain homeostasis of thymically-derived and peripherally-derived Treg cells.

Suggested Citation

  • Tom Sidwell & Yang Liao & Alexandra L. Garnham & Ajithkumar Vasanthakumar & Renee Gloury & Jonas Blume & Peggy P. Teh & David Chisanga & Christoph Thelemann & Fabian Labastida Rivera & Christian R. En, 2020. "Attenuation of TCR-induced transcription by Bach2 controls regulatory T cell differentiation and homeostasis," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14112-2
    DOI: 10.1038/s41467-019-14112-2
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    Cited by:

    1. Robin D. Lee & Sarah A. Munro & Todd P. Knutson & Rebecca S. LaRue & Lynn M. Heltemes-Harris & Michael A. Farrar, 2021. "Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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