Jain, R;
Zhao, K;
Sheridan, JM;
Heinlein, M;
Kupresanin, F;
Abeysekera, W;
Hall, C;
... Gray, DHD; + view all
(2021)
Dual roles for LUBAC signaling in thymic epithelial cell development and survival.
Cell Death & Differentiation
, 28
(10)
pp. 2946-2956.
10.1038/s41418-021-00850-8.
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Abstract
Thymic epithelial cells (TECs) form a unique microenvironment that orchestrates T cell differentiation and immunological tolerance. Despite the importance of TECs for adaptive immunity, there is an incomplete understanding of the signalling networks that support their differentiation and survival. We report that the linear ubiquitin chain assembly complex (LUBAC) is essential for medullary TEC (mTEC) differentiation, cortical TEC survival and prevention of premature thymic atrophy. TEC-specific loss of LUBAC proteins, HOIL-1 or HOIP, severely impaired expansion of the thymic medulla and AIRE-expressing cells. Furthermore, HOIL-1-deficiency caused early thymic atrophy due to Caspase-8/MLKL-dependent apoptosis/necroptosis of cortical TECs. By contrast, deficiency in the LUBAC component, SHARPIN, caused relatively mild defects only in mTECs. These distinct roles for LUBAC components in TECs correlate with their function in linear ubiquitination, NFκB activation and cell survival. Thus, our findings reveal dual roles for LUBAC signaling in TEC differentiation and survival.
| Type: | Article |
|---|---|
| Title: | Dual roles for LUBAC signaling in thymic epithelial cell development and survival |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41418-021-00850-8 |
| Publisher version: | https://doi.org/10.1038/s41418-021-00850-8 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Cell Biology, LINEAR UBIQUITIN, CROSS-TALK, T-CELLS, SHARPIN, COMPLEX, LIGASE, IMMUNODEFICIENCY, AUTOINFLAMMATION, AMYLOPECTINOSIS, INFLAMMATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10142394 |
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