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

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)-...

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Detalles Bibliográficos
Autores principales: Teh, Charis E., Lalaoui, Najoua, Jain, Reema, Policheni, Antonia N., Heinlein, Melanie, Alvarez-Diaz, Silvia, Sheridan, Julie M., Rieser, Eva, Deuser, Stefanie, Darding, Maurice, Koay, Hui-Fern, Hu, Yifang, Kupresanin, Fiona, O'Reilly, Lorraine A., Godfrey, Dale I., Smyth, Gordon K., Bouillet, Philippe, Strasser, Andreas, Walczak, Henning, Silke, John, Gray, Daniel H. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120208/
https://www.ncbi.nlm.nih.gov/pubmed/27857075
http://dx.doi.org/10.1038/ncomms13353
Descripción
Sumario: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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