Survival of mature T cells depends on signaling through HOIP

• 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; https://dl.ndl.go.jp/pid/10951840
• 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
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/112366
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