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

被引：0

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.

引用

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