Medical Biology - Research Publications

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Author: Strasser, Andreas × Author: Alvarez-Diaz, Silvia × Author: Gray, Daniel ×

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    The linear ubiquitin chain assembly complex: a new function in thymic T cell differentiation and regulatory T cell homeostasis
    Teh, C ; Lalaoui, N ; Jain, R ; Policheni, A ; Heinlein, M ; Alvarez-Diaz, S ; Rieser, E ; Deuser, S ; Koay, H-F ; Hu, Y ; Kupresanin, F ; O'Reilly, L ; Godfrey, D ; Smyth, G ; Bouillet, P ; Strasser, A ; Walczak, H ; Silke, J ; Gray, D (WILEY-BLACKWELL, 2016-08-01)
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    Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis
    Teh, CE ; Lalaoui, N ; Jain, R ; Policheni, AN ; Heinlein, M ; Alvarez-Diaz, S ; Sheridan, JM ; Rieser, E ; Deuser, S ; Darding, M ; Koay, H-F ; Hu, Y ; Kupresanin, F ; O'Reilly, LA ; Godfrey, DI ; Smyth, GK ; Bouillet, P ; Strasser, A ; Walczak, H ; Silke, J ; Gray, DHD (NATURE PUBLISHING GROUP, 2016-11-18)
    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.