Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms13353
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Funding
- Australian NHMRC grants [1078763, 1049724, 1083942, 1013667, 1016701, 1046010, 602516, 104984, 1057905, 1058190, 1089072, 1090236, 1020770]
- Cancer Australia [1047672]
- Leukemia and Lymphoma Society (SCOR grant) [7413, 7001-13]
- Australian Research Council (ARC) [CE140100011, LE110100106]
- Wellcome Trust Senior Investigator Award [096831/Z/11/Z]
- ERC Advanced grant [294880]
- Wellcome Trust [096831/Z/11/Z] Funding Source: Wellcome Trust
- National Health and Medical Research Council of Australia [1057905, 1089072, 1078763, 1083942, 1058190, 1090236] Funding Source: NHMRC
- European Research Council (ERC) [294880] Funding Source: European Research Council (ERC)
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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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