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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/85148完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 江伯倫(Bor-Luen Chiang) | |
| dc.contributor.author | Tzu-Yun Liu | en |
| dc.contributor.author | 劉姿昀 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:46:35Z | - |
| dc.date.copyright | 2022-10-04 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-08-10 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/85148 | - |
| dc.description.abstract | 調節型T細胞是抑制免疫反應的有效細胞，並在免疫恆定上扮演很重要的角色。干擾素(Interferon)是常見的細胞激素，也被發現會影響調節性T細胞Foxp3的表達和抑制能力。干擾素誘導的GTP酶(Interferon-inducible GTPase)是會顯著被干擾素誘導的蛋白，此外在文獻中也指出這些蛋白和調節性T細胞上的調節性分子有關連性。在我們實驗室先前的研究中發現，B細胞可以誘導T 細胞轉變成一群具有免疫調控功能的T 細胞，我們將其命名為B細胞誘發的調節性T細胞 (Treg-of-B)。根據Treg-of-B細胞的單細胞轉錄組學(single-cell sequencing)也顯示這些細胞在interferon-inducible GTPase的表達較其他抗原所誘導的T細胞高。但我們發現與Treg-of-B細胞相比，天然調節性T細胞在這些基因中的表達較高。根據這些結果我們初步得知，interferon-inducible GTPase在天然調節性T細胞中可能較為重要。然而並沒有過多的研究探討interferon-inducible GTPase在調控調節性T細胞的抑制能力中的角色。因此接下來我們深入研究interferon-inducible GTPase在天然調節性T細胞的抑制能力中的角色。我們首先確定這些蛋白在天然調節性T細胞中的表達，在刺激的狀態下guanylate-binding protein家族的基因表現量較其他家族顯著上升。接著用RNA干擾技術下調guanylate-binding protein的表現量，觀察其對天然調節性T細胞表型及功能的影響，發現在Gbp2的基因表現下降時，Treg相關的基因如Foxp3、IL-10等也有表現量下降的情形。IL-10、IFN-γ及IL-17等細胞激素的分泌和抑制細胞增生的能力也在Gbp2表現量下降時受到影響。本篇研究發現Gbp2在nTreg中扮演角色，並和調節型T 細胞的免疫調節有關係。 | zh_TW |
| dc.description.abstract | Regulatory T (Treg) cells are effective immune cells for suppressing the abnormal immune response and play the important role in immune homeostasis. Interferons (IFNs) are well-known cytokines. Interferon-inducible GTPases, significantly induced by interferon, are also related to regulatory molecules of Treg cells. Our previous studies found that B cells could induce nave CD4+ CD25- T cells into CD4+ CD25+ Foxp3- regulatory T cells termed Treg-of-B cells. The single-cell sequencing of Treg-of-B cells also showed that the expressions of interferon-inducible GTPases were higher than that of other T cells subsets. We further found that nTreg cells have even higher expression of these genes compared with Treg-of-B cells. These findings showed that the interferon-inducible GTPases might be more important in nTreg cells. And then we focused on the expression of these proteins in nTreg cells, the gene expression of the Guanylate-binding protein (Gbps) family was significantly increased in the stimulated state. We used RNA interference technology to knockdown the expression of Gbp family. After optimizing the transfection conditions, the expression of Gbp2 significantly decreased, and the expression of Treg-related genes, like Foxp3 and IL-10, also declined. The cytokine level of IL-10, IFN-γ, and IL-17 and the suppressive function of Foxp3+ nTreg cells were also affected when the expression of Gbp2 decreased. In this study, we revealed a novel role for Gbp2 in nTreg cells and suggested the correlation of Gbp2 and the immunoregulatory function in Treg cells. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:46:35Z (GMT). No. of bitstreams: 1 U0001-0908202216301200.pdf: 1596558 bytes, checksum: 76ab8e987d84ccbf106e510f22610541 (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員審定書 i 謝辭 ii 中文摘要 iv Abstract v Contents vii Chapter I Introduction 1 1. Background 2 1.1 T cell differentiation 2 1.2 Regulatory T cells (Treg) 2 1.3 Regulatory T cells population 4 1.4 Regulatory T cells induced by B cells 5 1.5 Interferon (IFN)-inducible GTPase and other GTPase-related genes 5 1.6 GTPase and regulatory T cells 6 2. Hypothesis and specific aims 7 Chapter II Materials and Methods 9 1. Materials 10 1.1 Animals 10 1.2 Culture medium 10 1.3 Buffer 10 1.4 EasySepTM system 11 1.5 BD IMagTM system 11 1.6 Monoclonal antibodies (mAbs) 11 1.7 Flow cytometry 12 1.8 [3H]-incorporation assay 12 1.9 Enzyme-linked immunosorbent assay (ELISA) 13 1.10 RNA extraction 13 1.11 Real-time polymerase chain reaction (quantitative PCR, qPCR) 14 1.12 siRNA transfection 17 2. Methods 17 2.1 Preparation of splenocytes 17 2.2 B220+ and CD4+CD25- T cell isolation 18 2.3 In vitro generation of Treg-of-B cells 19 2.4 Re-stimulation of CD4+CD25- T cells, Treg-of-B cells, and nTreg cells 19 2.5 Flow cytometry analysis 19 2.6 [3H]-incorporation assay 20 2.7 Cytokine analysis 20 2.8 mRNA extraction 21 2.9 Reverse transcription polymerase chain reaction (RT-PCR) for mRNA 22 2.10 Real-time polymerase chain reaction (quantitative PCR, qPCR) 22 2.11 siRNA transfection 23 2.12 Statistical analysis 23 Chapter III Results 24 1.The purity of B220+ B, CD4+ CD25- T cells, and CD4+ CD25+ T cells 25 2.Surface molecules expression of Treg-of-B cells and CD4+CD25+ T cells 25 3.Suppressive capacity and cytokine profiles of Treg-of-B cells and CD4+ CD25+ T cells 26 4.The single-cell RNA-sequencing analysis of Treg-of-B, T-of-OB1 cells, and T-of-DC 27 5.The GTPase-related gene expression of nTreg cells and Treg-of-B cells in the resting state 27 6.The GTPase-related gene expression of nTreg cells in resting and stimulated state 28 7.Fluorescent-conjugated control siRNA was used to determine the transfection efficiency of T cells 28 8. Knockdown of Gbp2 attenuated the expression of Treg-related genes in CD4+CD25+ nTreg cells after IFN-γ restimulation 29 9.Cytokine profile of CD4+CD25+ nTreg cells changed after guanylate binding proteins family siRNA transfection 30 10.Gbp2 knockdown seems to affect the suppressive function of CD4+CD25+ nTreg cells 30 Chapter IV Discussion 31 Figures 38 Figure 1. The purity of B220+ B, CD4+ CD25- T cells, and CD4+ CD25+ T cells 39 Figure 2. Surface molecules expression of Treg-of-B cells and CD4+CD25+ T cells 40 Figure 3. Suppressive capacity and cytokine profiles of Treg-of-B cells and CD4+ CD25+ T cells 42 Figure 4. The single-cell RNA-sequencing analysis of Treg-of-B, T-of-OB1 cells, and T-of-DC 44 Figure 5. The GTPase-related gene expression of nTreg cells and Treg-of-B cells in the resting state 46 Figure 6. The GTPase-related gene expression of nTreg cells in resting and stimulated state 47 Figure 7. Fluorescent-conjugated control siRNA was used to determine the transfection efficiency of T cells 48 Figure 8. Knockdown of Gbp2 attenuated the expression of Treg-related genes in CD4+CD25+ nTreg cells after IFN-γ restimulation 50 Fig 9. Cytokine profile of CD4+CD25+ nTreg cells changed after guanylate binding proteins family siRNA transfection 51 Fig 10. Gbp2 knockdown seems to affect the suppressive function of CD4+CD25+ nTreg cells 52 References 53 Supplement 59 Supplementary figure 1. Autophagy-associated gene expression of CD4+CD25- T cells, CD4+CD25+ nTreg and Treg-of-B cells 60 | |
| dc.language.iso | en | |
| dc.subject | 干擾素誘導的GTP酶 | zh_TW |
| dc.subject | 天然調節性T細胞 | zh_TW |
| dc.subject | B細胞誘發的調節性T細胞 | zh_TW |
| dc.subject | Interferon-inducible GTPase | en |
| dc.subject | natural regulatory T cells | en |
| dc.subject | Treg-of-B cells | en |
| dc.title | 探討鳥苷酸結合蛋白在調節性T細胞功能中所扮演的角色 | zh_TW |
| dc.title | The Role of Guanylate-Binding Protein in the Function of Regulatory T Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林志萱(Jr-Shiuan Lin),楊宏志(Hung-Chih Yang) | |
| dc.subject.keyword | 天然調節性T細胞,B細胞誘發的調節性T細胞,干擾素誘導的GTP酶, | zh_TW |
| dc.subject.keyword | natural regulatory T cells,Treg-of-B cells,Interferon-inducible GTPase, | en |
| dc.relation.page | 60 | |
| dc.identifier.doi | 10.6342/NTU202202213 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-08-10 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| dc.date.embargo-lift | 2023-08-31 | - |
| 顯示於系所單位： | 免疫學研究所 | |
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