Dual roles for LUBAC signaling in thymic epithelial cell development and survival.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
17
02
2021
accepted:
02
08
2021
revised:
26
07
2021
pubmed:
13
8
2021
medline:
26
3
2022
entrez:
12
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34381167
doi: 10.1038/s41418-021-00850-8
pii: 10.1038/s41418-021-00850-8
pmc: PMC8481470
doi:
Substances chimiques
Ubiquitin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2946-2956Subventions
Organisme : Wellcome Trust
ID : 214342/Z/18/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A27323
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S00811X/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.
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