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Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis

Author

Listed:
  • Charis E. Teh

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

  • Najoua Lalaoui

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

  • Reema Jain

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

  • Antonia N. Policheni

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

  • Melanie Heinlein

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

  • Silvia Alvarez-Diaz

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

  • Julie M. Sheridan

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

  • Eva Rieser

    (Centre for Cell Death, Cancer and Inflammation, University College London)

  • Stefanie Deuser

    (Centre for Cell Death, Cancer and Inflammation, University College London)

  • Maurice Darding

    (Centre for Cell Death, Cancer and Inflammation, University College London)

  • Hui-Fern Koay

    (The Peter Doherty Institute for Infection and Immunity, The University of Melbourne
    The Australian Research Council Centre of Excellence for Advanced Molecular Imaging, The University of Melbourne)

  • Yifang Hu

    (The Walter and Eliza Hall Institute of Medical Research)

  • Fiona Kupresanin

    (The Walter and Eliza Hall Institute of Medical Research
    Present address: ANZAC Research Institute, Concord Repatriation General Hospital, Concord, New South Wales 2139, Australia)

  • Lorraine A. O’Reilly

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

  • Dale I. Godfrey

    (The Peter Doherty Institute for Infection and Immunity, The University of Melbourne
    The Australian Research Council Centre of Excellence for Advanced Molecular Imaging, The University of Melbourne)

  • Gordon K. Smyth

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

  • Philippe Bouillet

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

  • Andreas Strasser

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

  • Henning Walczak

    (Centre for Cell Death, Cancer and Inflammation, University College London)

  • John Silke

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

  • Daniel H. D. Gray

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

Abstract

The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role in adaptive immunity is unclear. Here we show that the LUBAC components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3+ regulatory T (Treg)-cell development and Treg cell homeostasis. LUBAC activity is not required to prevent TNF-induced apoptosis or necroptosis but is necessary for the transcriptional programme of the penultimate stage of thymocyte differentiation. Treg cell-specific ablation of HOIP causes severe Treg cell deficiency and lethal immune pathology, revealing an ongoing requirement of LUBAC activity for Treg cell homeostasis. These data reveal stage-specific requirements for LUBAC in coordinating the signals required for T-cell differentiation.

Suggested Citation

  • Charis E. Teh & Najoua Lalaoui & Reema Jain & Antonia N. Policheni & Melanie Heinlein & Silvia Alvarez-Diaz & Julie M. Sheridan & Eva Rieser & Stefanie Deuser & Maurice Darding & Hui-Fern Koay & Yifan, 2016. "Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13353
    DOI: 10.1038/ncomms13353
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    Cited by:

    1. Yesheng Fu & Lei Li & Xin Zhang & Zhikang Deng & Ying Wu & Wenzhe Chen & Yuchen Liu & Shan He & Jian Wang & Yuping Xie & Zhiwei Tu & Yadi Lyu & Yange Wei & Shujie Wang & Chun-Ping Cui & Cui Hua Liu & , 2024. "Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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