Survival of mature T cells depends on signaling through HOIP

Persistent ID (NDL): info:ndljp/pid/10951840

Material type: 博士論文

Author: Okamura, Kazumiほか

Publisher: Springer Nature

Publication date: 2016-10-27

Material Format: Digital

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Name of awarding university/degree: 徳島大学,博士（医学）

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Note (General)：: 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 ...

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Material Type: 博士論文
ISSN: 2045-2322
Title: Survival of mature T cells depends on signaling through HOIP
Volume: 6
Author/Editor: Okamura, Kazumi
Kitamura, Akiko
Sasaki, Yoshiteru
Chung, Doo Hyun
Kagami, Shoji
Iwai, Kazuhiro
Yasutomo, Koji
Author Heading: Okamura, Kazumi
Kitamura, Akiko
Sasaki, Yoshiteru
Chung, Doo Hyun
Kagami, Shoji
Iwai, Kazuhiro
Yasutomo, Koji
Publication, Distribution, etc.: Springer Nature
Publication Date: 2016-10-27
Publication Date (W3CDTF): 2016-10-27
Alternative Title: 成熟T細胞の生存はHOIPを介するシグナルに依存する
Periodical title: Scientific Reports
Degree grantor/type: 徳島大学
Date Granted: 2017-02-23
Date Granted (W3CDTF): 2017-02-23
Dissertation Number: 甲第3010号
Degree Type: 博士（医学）
Conferring No. (Dissertation): 甲第3010号
Text Language Code: eng
Subject Heading: HOIP
LUBAC complex
ligase activity
NFκB
cell survival
Target Audience: 一般
Note (General): 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.
DOI: info:doi/10.1038/srep36135
https://doi.org/info:doi/10.1038/srep36135
Persistent ID (NDL): info:ndljp/pid/10951840
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Collection: 障害者向け資料
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Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
https://dl.ndl.go.jp/collections/A00014
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2017-09-02T15:28:24+09:00
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
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Availability of remote photoduplication service: 可
Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/112366
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