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DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 顏伯勳(Bo-Shiun Yan) | |
dc.contributor.advisor | 顏伯勳(Bo-Shiun Yan | bsyan@ntu.edu.tw | ), | |
dc.contributor.author | Yi-Lun Chen | en |
dc.contributor.author | 陳奕倫 | zh_TW |
dc.date.accessioned | 2023-03-19T22:13:04Z | - |
dc.date.copyright | 2022-10-13 | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022-09-26 | |
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Jia-Shiun Leu, M.-L.C., So-Yi Chang, Sung-Liang Yu, Chia-Wei Lin, Hsuan Wang, Wan-Chen Chen,3 Chin-Hao Chang,5 Jann-Yuan Wang, Li-Na Lee, Chong-Jen Yu, Igor Kramnik, and Bo-Shiun Yan, SP110b Controls Host Immunity and Susceptibility to Tuberculosis, in Am J Respir Crit Care Med 2017. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84484 | - |
dc.description.abstract | 全世界約有四分之一的人感染了結核分枝桿菌 (Mtb),但其中只有不到 10% 的感染者發展為結核病 (TB)。宿主遺傳因子已被證明會影響 Mtb 感染結果。SP110 是一種干擾素誘導的核蛋白,屬於 SP110/SP140 蛋白家族。 SP110b 是 SP110 表現最多的異構體,已被證明可控制宿主免疫和結核病的易感性 (susceptibility)。此外,我們之前的研究顯示,SP110b 在 Mtb 感染期間調節巨噬細胞和單核細胞產生的細胞激素 (cytokines) 和趨化素 (chemokines) 的表現。在 TB 發病過程中,T 細胞不斷被活化以誘導巨噬細胞轉移到感染部位並形成肉芽腫 (granuloma),這顯示它們對於防止 Mtb 感染極為重要並且是必需的。細胞激素白細胞介素 2 (IL-2) 主要是通過其對 T 細胞的影響而在免疫系統中發揮重要作用,因此,適當調節 IL-2 的表現對於免疫系統保護宿主免受 Mtb 感染很重要。 IL-2 基因的表現受到多種途徑的嚴格調控,包括三種主要轉錄因子(NF-AT、NF-kB 和 AP-1)及其途徑。在本研究中,我們利用誘導後表現 SP110b 的 Jurkat T 細胞株來研究在T 細胞中 SP110b 介導之 IL-2 表現的調控,並進一步了解 SP110b 介導的調控對 T 細胞功能的影響。結果顯示 SP110b 會抑制 IL-2 的表現,進而去抑制 T 細胞的增殖。這意味著SP110蛋白除了可以調控單核細胞/巨噬細胞外,還可以調控 T 細胞以控制宿主對於 Mtb 感染時的免疫反應。 | zh_TW |
dc.description.abstract | There are about one quarter of people infected with Mycobacterium tuberculosis (Mtb) in the world, yet less than 10% become ill with tuberculosis (TB). Host genetic factors have been shown to influence Mtb infection outcomes. SP110 is an interferon-induced nuclear protein that belongs to the SP110/SP140 protein family. In our previous studies, SP110b, the most dominantly expressed isoform of SP110, has been shown to control host immunity and TB susceptibility. We also demonstrated that SP110b regulated the expression of cytokines and chemokines produced by macrophages and monocytes during Mtb infection. During TB pathogenesis, T cells keep activating to induce macrophage migration into the infected sites where granulomas are formed, indicating that they are critical and needed for protection against Mtb infection. The cytokine interleukin-2 (IL-2) plays an essential role in the immune system, mainly via its effects on T cells. Therefore, a proper regulation for IL-2 expression is important for the immune system to protect against Mtb infection. The expression of the IL-2 gene is tightly regulated by multiple pathways, including three major transcription factors (NFAT, NFkB and AP-1) and their pathways. In the study, we used Jurkat T cell clones that over-express SP110b upon induction to investigate the SP110b-mediated regulation of the IL-2 expression in T cells and further determine the effect of the SP110b-mediated regulation on T cells. The results demonstrate that SP110b down-regulates IL-2 expression thereby suppressing proliferation of T cells. It implies that SP110 protein, in addition to regulating monocytes/macrophages, may also regulate T cells in order to control host immunity against Mtb infection. | en |
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dc.description.tableofcontents | 誌謝 i 中文摘要 ii Abstract iii 目錄 iv 圖目錄 vii 表目錄 viii 第一章 緒論 1 1.1 Tuberculosis(TB) 1 1.2 TB和SP110之間的關聯 4 1.3 SP110b 4 1.4 T cell immune response in TB program 6 1.5 Jurkat cell 7 1.6 Interleukin 2(IL-2)and IL-2 receptor alpha 7 1.7 Specific Aim 8 第二章 材料與方法 9 2.1 Plasmid 9 2.2 細胞株培養(Cell culture) 10 2.3 藥物處理(Drug treatment) 11 2.3.1 去氧羥四環素(Doxycycline;DOX) 11 2.3.2 佛波肉荳蔻酸酯醋酸酯(PMA;Phorbol myristate acetate) 11 2.3.3 離子黴素(Calcium ionophore;Ionomycin) 11 2.3.4 植物血凝素(PHA-P;Phytohaemagglutinin P) 12 2.4 西方點墨法(western blot) 12 2.5 核糖核酸萃取(RNA extraction) 15 2.6 反轉錄反應(reverse transcription;RNA轉成cDNA) 16 2.7 即時定量聚合酶連鎖反應(Quantitative real-time polymerase chain reaction) 17 2.8 Generation of lentivirus 17 2.9 Lentivirus Transduction 18 2.10 Fluorescence Assay 19 2.11 Neon Transfection System 19 2.12 Luciferase Reporter Assay 20 2.13 T cell proliferation assay 21 2.14 統計分析(Statistical analysis) 21 第三章 實驗結果 23 3.1 Jurkat cell clones stably over-expresses eGFP-SP110b upon DOX induction 23 3.2 IL-2 expression is down-regulated in the presence of SP110b expression 24 3.3 IL-2 receptor-alpha expression is down-regulated in the presence of SP110b expression 26 3.4 IL-2 promoter is down-regulated in the presence of SP110b expression 26 3.5 T cell proliferation is down-regulated in the presence of SP110b 27 第四章 討論 28 附錄 32 圖一、急性T細胞白血病細胞株誘導表現SP110b 32 圖二、T細胞利用doxycycline誘導表現SP110b的共軛顯微鏡觀察 34 圖三、T細胞在受到藥物刺激的同時誘導表現SP110b 36 圖四、SP110b對於IL-2和IL-2Ra表現量的影響 38 圖五、SP110b對於IL-2蛋白表現量的影響 40 圖六、SP110b對於IL-2和IL-2Ra的RNA表現量的影響 42 圖七、SP110b對於刺激時間不同的IL-2表現量的影響 44 圖八、SP110b對於IL-2 promoter的影響 47 圖九、SP110b對於T細胞增生的影響 49 參考文獻 50 附表 57 表一、本研究使用的引子序列 57 表二、IL-2啟動子序列 57 表三、本研究使用的抗體清單 58 | |
dc.language.iso | zh-TW | |
dc.title | SP110b 核蛋白調控IL-2的表現和T細胞的細胞增殖 | zh_TW |
dc.title | SP110b nuclear protein regulates IL-2 expression and T cell proliferation | en |
dc.type | Thesis | |
dc.date.schoolyear | 110-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 詹世鵬(Shih-Peng Chan),蘇剛毅(Kang-Yi Su) | |
dc.subject.keyword | SP110,T細胞,IL-2,轉錄調控, | zh_TW |
dc.subject.keyword | SP110,T cell,IL-2,transcriptional regulation, | en |
dc.relation.page | 58 | |
dc.identifier.doi | 10.6342/NTU202203921 | |
dc.rights.note | 同意授權(限校園內公開) | |
dc.date.accepted | 2022-09-26 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
dc.date.embargo-lift | 2022-10-13 | - |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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