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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
Author
Sasaki, Yoshiteru Kyoto University
Chung, Doo Hyun Seoul National University
Iwai, Kazuhiro Kyoto University
Yasutomo, Koji Tokushima University|Japan Agency for Medical Research and Development Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
HOIP
LUBAC complex
ligase activity
NFκB
cell survival
Content Type
Thesis or Dissertation
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.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
6
Start Page
36135
Published Date
2016-10-27
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
TextVersion
ETD
MEXT report number
甲第3010号
Diploma Number
甲医第1314号
Granted Date
2017-02-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences