Universität zu Köln

Jain, Reema, Zhao, Kelin, Sheridan, Julie M., Heinlein, Melanie, Kupresanin, Fiona, Abeysekera, Waruni, Hall, Cathrine, Rickard, James, Bouillet, Philippe, Walczak, Henning ORCID: 0000-0002-6312-4591, Strasser, Andreas ORCID: 0000-0002-5020-4891, Silke, John and Gray, Daniel H. D. (2021). Dual roles for LUBAC signaling in thymic epithelial cell development and survival. Cell Death Differ., 28 (10). S. 2946 - 2957. LONDON: SPRINGERNATURE. ISSN 1476-5403

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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, NF kappa B activation and cell survival. Thus, our findings reveal dual roles for LUBAC signaling in TEC differentiation and survival.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jain, Reema UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhao, Kelin UNSPECIFIED UNSPECIFIED UNSPECIFIED Sheridan, Julie M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinlein, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kupresanin, Fiona UNSPECIFIED UNSPECIFIED UNSPECIFIED Abeysekera, Waruni UNSPECIFIED UNSPECIFIED UNSPECIFIED Hall, Cathrine UNSPECIFIED UNSPECIFIED UNSPECIFIED Rickard, James UNSPECIFIED UNSPECIFIED UNSPECIFIED Bouillet, Philippe UNSPECIFIED UNSPECIFIED UNSPECIFIED Walczak, Henning UNSPECIFIED orcid.org/0000-0002-6312-4591 UNSPECIFIED Strasser, Andreas UNSPECIFIED orcid.org/0000-0002-5020-4891 UNSPECIFIED Silke, John UNSPECIFIED UNSPECIFIED UNSPECIFIED Gray, Daniel H. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-598290
DOI:	10.1038/s41418-021-00850-8
Journal or Publication Title:	Cell Death Differ.
Volume:	28
Number:	10
Page Range:	S. 2946 - 2957
Date:	2021
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1476-5403
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LINEAR UBIQUITIN; CROSS-TALK; T-CELLS; SHARPIN; COMPLEX; LIGASE; IMMUNODEFICIENCY; AUTOINFLAMMATION; AMYLOPECTINOSIS; INFLAMMATION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59829