AI Article Synopsis
- Thymic epithelial cells (TECs) create a specialized environment crucial for T cell development and immune tolerance, but the molecular processes governing their growth and survival remain unclear.
- The study identifies the linear ubiquitin chain assembly complex (LUBAC) as vital for the differentiation of medullary TECs and the survival of cortical TECs, with specific LUBAC proteins showing different impacts on thymic functions.
- Loss of certain LUBAC components leads to severe issues such as thymic atrophy and impaired TEC development, highlighting the importance of LUBAC signaling in both TEC differentiation and overall cell survival.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481470 | PMC |
| http://dx.doi.org/10.1038/s41418-021-00850-8 | DOI Listing |
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