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

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作者：
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
Yifang Hu
Fiona Kupresanin
Lorraine A. O’Reilly
Dale I. Godfrey
Gordon K. Smyth
Philippe Bouillet
Andreas Strasser
Henning Walczak
John Silke
Daniel H. D. Gray
机构：
[1] The Walter and Eliza Hall Institute of Medical Research,Department of Medical Biology
[2] The University of Melbourne,The Department of Microbiology and Immunology
[3] Centre for Cell Death,Department of Mathematics and Statistics
[4] Cancer and Inflammation,undefined
[5] University College London,undefined
[6] The Peter Doherty Institute for Infection and Immunity,undefined
[7] The University of Melbourne,undefined
[8] The Australian Research Council Centre of Excellence for Advanced Molecular Imaging,undefined
[9] The University of Melbourne,undefined
[10] The University of Melbourne,undefined
[11] Present address: ANZAC Research Institute,undefined
[12] Concord Repatriation General Hospital,undefined
[13] Concord,undefined
[14] New South Wales 2139,undefined
[15] Australia,undefined
来源：
Nature Communications | / 7卷
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摘要：
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.
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