Dual roles for LUBAC signaling in thymic epithelial cell development and survival
- Author(s)
- Jain, R; Zhao, K; Sheridan, JM; Heinlein, M; Kupresanin, F; Abeysekera, W; Hall, C; Rickard, J; Bouillet, P; Walczak, H; Strasser, A; Silke, J; Gray, DHD;
- Details
- Publication Year 2021-08-11,Volume 28,Issue #10,Page 2946-2956
- Journal Title
- Cell Death and Differentiation
- 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.
- Publisher
- NPG
- Research Division(s)
- Immunology; Bioinformatics; Inflammation; Blood Cells And Blood Cancer
- PubMed ID
- 34381167
- Publisher's Version
- https://doi.org/10.1038/s41418-021-00850-8
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-09-17 09:11:58
Last Modified: 2022-02-21 11:16:52