Survival of mature T cells depends on signaling through HOIP

• Material Type: 博士論文
• Title: Survival of mature T cells depends on signaling through HOIP
• 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
• No. or year of volume/issue: 6
• Volume: 6
• Pages: 36135-
• ISSN (Periodical Title): ISSN : 2045-2322
• Degree grantor/type: 徳島大学
• Date Granted: 2017-02-23
• Dissertation Number: 甲第3010号
• Degree Type: 博士（医学）
• 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © 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/
• Related Material (DOI): 10.1038/srep36135
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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