ID | 112366 |
Title Alternative | 成熟T細胞の生存はHOIPを介するシグナルに依存する
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Author |
Okamura, Kazumi
Tokushima University
Tokushima University Educator and Researcher Directory
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Sasaki, Yoshiteru
Kyoto University
Chung, Doo Hyun
Seoul National University
Kagami, Shoji
Tokushima University
Tokushima University Educator and Researcher Directory
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Iwai, Kazuhiro
Kyoto University
Yasutomo, Koji
Tokushima University|Japan Agency for Medical Research and Development
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Keywords | HOIP
LUBAC complex
ligase activity
NFκB
cell survival
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Content Type |
Thesis or Dissertation
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Description | T cell development in the thymus is controlled by a multistep process. The NF-κB pathway regulates T cell development as well as T cell activation at multiple differentiation stages. The linear ubiquitin chain assembly complex (LUBAC) is composed of Sharpin, HOIL-1L and HOIP, and it is crucial for regulating the NF-κB and cell death pathways. However, little is known about the roles of LUBAC in T-cell development and activation. Here, we show that in T-HOIPΔlinear mice lacking the ubiquitin ligase activity of LUBAC, thymic CD4+ or CD8+ T cell numbers were markedly reduced with severe defects in NKT cell development. HOIPΔlinear CD4+ T cells failed to phosphorylate IκBα and JNK through T cell receptor-mediated stimulation. Mature CD4+ and CD8+ T cells in T-HOIPΔlinear mice underwent apoptosis more rapidly than control T cells, and it was accompanied by lower CD127 expression on CD4+CD24low and CD8+CD24low T cells in the thymus. The enforced expression of CD127 in T-HOIPΔlinear thymocytes rescued the development of mature CD8+ T cells. Collectively, our results showed that LUBAC ligase activity is key for the survival of mature T cells, and suggest multiple roles of the NF-κB and cell death pathways in activating or maintaining T cell-mediated adaptive immune responses.
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Journal Title |
Scientific Reports
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ISSN | 20452322
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Publisher | Springer Nature
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Volume | 6
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Start Page | 36135
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Published Date | 2016-10-27
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Remark | 内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201704271003.pdf 論文本文:k3010_fulltext.pdf 本論文は,著者Kazumi Okamuraの学位論文として提出され,学位審査・授与の対象となっている。 |
Rights | © The Author(s) 2016
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3010号
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Diploma Number | 甲医第1314号
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Granted Date | 2017-02-23
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
University Hospital
Medical Sciences
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