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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 江伯倫 | zh_TW |
| dc.contributor.advisor | Bor-Luen Chiang | en |
| dc.contributor.author | 賴夢萱 | zh_TW |
| dc.contributor.author | Meng-Xuan Lai | en |
| dc.date.accessioned | 2023-09-26T16:21:03Z | - |
| dc.date.available | 2025-12-31 | - |
| dc.date.copyright | 2023-09-26 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-08-09 | - |
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Lentiviral vector induces high-quality memory T cells via dendritic cells transduction. Communications Biology, 4(1), 713. 89. Berger, G., Durand, S., Goujon, C., Nguyen, X. N., Cordeil, S., Darlix, J. L., & Cimarelli, A. (2011). A simple, versatile and efficient method to genetically modify human monocyte-derived dendritic cells with HIV-1-derived lentiviral vectors. Nature Protocols, 6(6), 806–816. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90342 | - |
| dc.description.abstract | 異位性皮膚炎(atopic dermatitis，AD)是一種會反覆發作過敏引起的慢性疾病，主要是會造成皮膚的病變，如：發炎、搔癢、紅腫、脹痛等症狀。全球約有10～20%的孩童受此疾病所苦。在AD的發病機制中，第二型輔助Ｔ細胞（Th2 cells）扮演重要角色，分泌介白素4（interleukin 4）與介白素13（interleukin 13）會抑制表皮分化和抑制表皮脂質生成，再次破壞皮膚屏障，並刺激B細胞分泌免疫球蛋白E (IgE)使肥大細胞致敏化，最後釋出組織胺介質而導致AD。目前已有抗IgE單株抗體藥物omalizuma和抗IL-4, IL-13 dupilumab，不過生物製劑的費用較為昂貴，因此我們想研究利用RNA干擾(RNAi)技術來研究治療。本研究將針對發病機制中關鍵的細胞激素IL-4和IL-13作為治療軸心，利用RNAi的技術幫助降解IL-4/IL-13的mRNA。實驗結果顯示，使用慢病毒載體遞送siRNA能有效地降低炎症細胞浸潤和減少發炎細胞激素IL-4，IL-13的表現，並進一步通過水凝膠混合帶有IL-4和IL-13的siRNA慢病毒載體敷至AD小鼠皮膚抑制基因的表現，實驗結果表明表現有顯著差異。未來，我們將選用微針技術更有效率地將siRNA遞送至小鼠做進一步的探討。本研究為AD的治療提供了新的思路和方法，有望成為治療AD的有效手段。 | zh_TW |
| dc.description.abstract | The goal of this research is to explore therapeutic strategies for atopic dermatitis (AD), a chronic disease caused by repeated allergic reactions, affecting approximately 10-20% of children worldwide. AD involves Th2 cells that release IL-4 and IL-13, which inhibit epidermal differentiation and suppress epidermal lipid synthesis, resulting in the impairment of the skin’s protective barrier. Mast cells become more sensitive or reactive due to the release of IgE antibodies. Ultimately, the release of histamine mediators cause AD. Currently, monoclonal antibodies against IgE, such as omalizumab and anti-IL-4R dupilumab are available, but they are quite expensive. Therefore, we aimed to explore the feasibility of RNA interference (RNAi) technology as a potential alternative. The study focused on targeting IL-4 and IL-13 of AD via RNAi to degrade their mRNA. The experimental results demonstrated that the use of a lentiviral vector to deliver siRNA can effectively reduce inflammatory cell infiltration and decrease IL-4 and IL-13 inflammatory cytokines. Moreover, the application of hydrogel mixed with lentiviral vectors carrying siRNA targeting IL-4 and IL-13 was employed to treat AD in mice, resulting in significant differences in the experimental outcomes. In the future, the study aims to investigate further the efficient delivery of siRNA to mice using microneedle technology. This study provides novel ideas and methods to address AD and might become a promising strategy to treating this disease. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-09-26T16:21:02Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-09-26T16:21:03Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 誌謝 I
中文摘要 III Abstract IV Contents VI Contents of figures XI Chapter 1. Introduction 1 Part1. Background 2 1. Atopic dermatitis 2 2. AD therapy Advance in AD treatment strategy 5 3. The mechanism of RNA interference 8 Part2. Hypothesis and specific aim 9 Chapter2. Materials and Methods 12 Part 1. Materials 13 1. Animals 13 2. Culture medium and buffer 13 3. Enzyme-linked immunosorbent assay (ELISA) 15 4. RNA extraction 15 5. Reverse transcriptase polymerase chain reaction (RT-PCR) 16 6. Real-time polymerase chain reaction / quantitative polymerase chain reaction (qPCR) 17 7. Flow cytometry 17 8. Immunohistochemical staining 17 9. Escherichia coli (E. coli) bacterial culturing and DNA extraction kit 17 10. Agarose gel electrophoresis, restriction enzyme and buffer 18 11. Preparation of shRNA-encoding lentivirus and treatment 18 12. The lentiviral titer was assessed by qPCR lentivirus titration kit 18 13. Ovalbumin-induced AD animal model 19 14. Therapeutics targeting IL-4 and IL-13 via lentiviral gene delivery in the skin of Ovalbumin-induced AD animal model 19 Part 2. Methods 20 1. Cell lines, cell culture and stimulation 20 2. Determination of EL4 cell line cytokine production 20 3. RNA extraction 21 4. cDNA synthesis and quantitative real-time PCR 22 5. Plasmids DNA prepared from E. coli bacteria 22 6. Plasmid DNA purification from E. coli by DNA extraction kit 23 7. Restriction Digest of Plasmid DNA 24 8. Agarose Gel Electrophoresis for the Separation of DNA Fragments 24 9. Determining RNA target sites and sequencing 25 10. Construction of shRNA lentiviral vector 25 11. The lentiviral titer was estimated by qPCR lentivirus titration kit 26 12. Determination of transfection efficiency by eGFP-lentivirus in EL4 T cell 26 13. Assessment of the inhibitory capacity of siIL-4 and siIL-13 in EL4 T cell 27 14. The murine model of ovalbumin-induced AD 27 15. Serum sample collection 28 16. Quantification of gene expression by mouse 29 17. Skin severity score 29 18. Histopathological studies 29 19. Hydrogel mixed with eGFP-lentivirus for OVA-induced AD model 30 20. Application of siIL-4 and siIL-13 lentivirus with hydrogel to the skin for OVA model 30 21. Statistical analysis 31 Chapter 3. Results 32 1. Lentiviral vector preparation and construction of plasmids 33 1.1 Genetic information transfection and plasmid construction 33 1.2 Utilized gel electrophoresis to identify the DNA fragment sizes in the lentiviral transfer plasmids 33 2. PMA + Ionomycin stimulation of IL-4 and IL-13 expression in EL-4 cell line 34 3. The most appropriate MOI formula to infect EL4 T cells 34 4. The delivery of lentivirus carrying siIL-4 effectively inhibited IL-4 formation in EL4 T cells. 35 5. Establishment of OVA-induced AD model 35 6. Skin severity score of AD 36 7. OVA-induced AD model triggered the induction of dermatitis resembling AD 36 8. The IgE level increased in OVA-induced AD model 37 9. OVA-induced AD caused inflammation 37 10. The mice were treated with a virus GFP-lentivirus to induce AD after exposure to OVA 38 11. The GFP-lentivirus hydrogel matrix is the most suitable therapeutic approach in our AD model 39 12. Dexamethasone, siIL-4, and siIL-13 significantly reduced epidermal thickness in AD model compared to the control group 40 Chapter 4. Discussion 42 Figures 49 References 64 | - |
| dc.language.iso | en | - |
| dc.subject | 第二型輔助Ｔ細胞 | zh_TW |
| dc.subject | 免疫球蛋白E | zh_TW |
| dc.subject | 慢病毒載體 | zh_TW |
| dc.subject | 異位性皮膚炎 | zh_TW |
| dc.subject | 基因沉默 | zh_TW |
| dc.subject | Atopic dermatitis | en |
| dc.subject | IgE | en |
| dc.subject | Lentivirus vector | en |
| dc.subject | T helper 2 cells | en |
| dc.subject | Gene silencing | en |
| dc.title | IL-4和IL-13的siRNA 對異位性皮膚炎動物模型的影響 | zh_TW |
| dc.title | Study on the effects of siRNA against IL-4 and IL-13 in animal model of atopic dermatitis | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.coadvisor | 侯欣翰 | zh_TW |
| dc.contributor.coadvisor | Hsin-Han Hou | en |
| dc.contributor.oralexamcommittee | 王麗潔;莊雅惠 | zh_TW |
| dc.contributor.oralexamcommittee | Li-Chieh Wang;Ya-Hui Chuang | en |
| dc.subject.keyword | 異位性皮膚炎,第二型輔助Ｔ細胞,慢病毒載體,免疫球蛋白E,基因沉默, | zh_TW |
| dc.subject.keyword | Atopic dermatitis,T helper 2 cells,Lentivirus vector,IgE,Gene silencing, | en |
| dc.relation.page | 82 | - |
| dc.identifier.doi | 10.6342/NTU202303855 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-08-10 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 口腔生物科學研究所 | - |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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