التفاصيل البيبلوغرافية
| العنوان: |
Nemo-like Kinase Drives Foxp3 Stability and Is Critical for Maintenance of Immune Tolerance by Regulatory T Cells |
| المؤلفون: |
Veerle Fleskens, Carlos M. Minutti, Xingmei Wu, Ping Wei, Cornelieke E.G.M. Pals, James McCrae, Saskia Hemmers, Vincent Groenewold, Harm-Jan Vos, Alexander Rudensky, Fan Pan, Huabin Li, Dietmar M. Zaiss, Paul J. Coffer |
| المصدر: |
Cell Reports, Vol 26, Iss 13, Pp 3600-3612.e6 (2019) |
| بيانات النشر: |
Elsevier, 2019. |
| سنة النشر: |
2019 |
| المجموعة: |
LCC:Biology (General) |
| مصطلحات موضوعية: |
Biology (General), QH301-705.5 |
| الوصف: |
Summary: The Foxp3 transcription factor is a crucial determinant of both regulatory T (TREG) cell development and their functional maintenance. Appropriate modulation of tolerogenic immune responses therefore requires the tight regulation of Foxp3 transcriptional output, and this involves both transcriptional and post-translational regulation. Here, we show that during T cell activation, phosphorylation of Foxp3 in TREG cells can be regulated by a TGF-β activated kinase 1 (TAK1)-Nemo-like kinase (NLK) signaling pathway. NLK interacts and phosphorylates Foxp3 in TREG cells, resulting in the stabilization of protein levels by preventing association with the STUB1 E3-ubiquitin protein ligase. Conditional TREG cell NLK-knockout (NLKΔTREG) results in decreased TREG cell-mediated immunosuppression in vivo, and NLK-deficient TREG cell animals develop more severe experimental autoimmune encephalomyelitis. Our data suggest a molecular mechanism, in which stimulation of TCR-mediated signaling can induce a TAK1-NLK pathway to sustain Foxp3 transcriptional activity through the stabilization of protein levels, thereby maintaining TREG cell suppressive function. : The maintenance of Foxp3 expression is critical for correct TREG cell function. Fleskens et al. demonstrate a molecular mechanism in which TCR engagement can stabilize Foxp3 protein expression through TAK1-NLK-regulated phosphorylation, thereby maintaining TREG cell suppressive function. Keywords: Foxp3, phosphorylation, regulatory T cell, NLK, TCR, ubiquitination, immune tolerance |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124719302736; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2019.02.087 |
| URL الوصول: |
https://doaj.org/article/8afbd001b6f74f43bf11390f6c3c68e8 |
| رقم الانضمام: |
edsdoj.8afbd001b6f74f43bf11390f6c3c68e8 |
| قاعدة البيانات: |
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