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

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 and Daniel H. D. Gray ()
Additional contact information
Charis E. Teh: The Walter and Eliza Hall Institute of Medical Research
Najoua Lalaoui: The Walter and Eliza Hall Institute of Medical Research
Reema Jain: The Walter and Eliza Hall Institute of Medical Research
Antonia N. Policheni: The Walter and Eliza Hall Institute of Medical Research
Melanie Heinlein: The Walter and Eliza Hall Institute of Medical Research
Silvia Alvarez-Diaz: The Walter and Eliza Hall Institute of Medical Research
Julie M. Sheridan: The Walter and Eliza Hall Institute of Medical Research
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
Yifang Hu: The Walter and Eliza Hall Institute of Medical Research
Fiona Kupresanin: The Walter and Eliza Hall Institute of Medical Research
Lorraine A. O’Reilly: The Walter and Eliza Hall Institute of Medical Research
Dale I. Godfrey: The Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Gordon K. Smyth: The Walter and Eliza Hall Institute of Medical Research
Philippe Bouillet: The Walter and Eliza Hall Institute of Medical Research
Andreas Strasser: The Walter and Eliza Hall Institute of Medical Research
Henning Walczak: Centre for Cell Death, Cancer and Inflammation, University College London
John Silke: The Walter and Eliza Hall Institute of Medical Research
Daniel H. D. Gray: The Walter and Eliza Hall Institute of Medical Research

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13353

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