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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 莊雅惠 | |
| dc.contributor.author | Yih-Mei Liou | en |
| dc.contributor.author | 劉羿梅 | zh_TW |
| dc.date.accessioned | 2021-06-15T12:39:22Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-07-28 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50404 | - |
| dc.description.abstract | 過敏性氣喘係因第二型輔助性T細胞的調控失調而造成。而間葉幹細胞除了細胞再生的能力之外同時具有免疫調控的能力而被視作一具有潛力的免疫治療。目前將間葉幹細胞應用在由OVA引起的氣喘小鼠動物模式上已有療效，但未有明確證據指出間葉幹細胞是否能直接抑制第二型輔助性T細胞的免疫反應以及間葉幹細胞對過敏性疾病病人的免疫的影響還並不是很清楚。首先我們利用培養的小鼠第二型輔助性T細胞和間葉幹細胞共同培養後發現小鼠第二型輔助性T細胞分泌細胞激素的功能有明顯的降低。接著將間葉幹細胞應用在過敏性氣喘的病患上以探討間葉幹細胞對於過敏疾病的影響。分析從過敏性氣喘病人血液樣本中分離出來的周邊血單核球細胞跟間葉幹細胞共同培養後的結果，發現其中T細胞的增生以及活化都受到抑制，同時由第二型輔助性T細胞分泌的細胞激素也有明顯的減低。而單一阻斷任一由間葉幹細胞產生的免疫抑制相關分子並不影響免疫抑制的結果，因此推斷參與間葉幹細胞進行免疫抑制應同時由多種分子調控。因此我們的實驗證實間葉幹細胞可以減低第二型輔助性T細胞的反應並且抑制過敏性氣喘病人的免疫反應。 | zh_TW |
| dc.description.abstract | Allergic asthma is an airway inflammation mediated by imbalanced type II helper T cell (Th2) immune response. Mesenchymal stem cell (MSC) is nowadays thought to be a potential immunotherapy. MSCs have been shown to suppress allergic asthma in ovalbumin immunized murine model. However, there is no clear evidence that MSCs can suppress Th2 cells directly and the effect of MSCs on allergic disease remains unclear. We cultured mouse Th2 cells to investigate the direct interaction between MSCs and Th2 cells. The result showed MSCs can efficiently suppress the cytokine production ability of Th2 cells. We applied MSCs to patients with allergic asthma to study the effect of MSCs on Th2 related disease. Utilizing peripheral blood mononuclear cells (PBMCs) isolated from asthma patients, we analyzed T cell proliferation and function after cocultured with MSCs and found that MSCs suppressed proliferation and Th2 cytokine production of T cells form asthma patients. This suppression phenotype might depend on multiple factors since blockade of single factor didn’t alter the suppressive effect of MSCs. In conclusion, MSCs is able to suppress the function of Th2 cells and also reduce T cell response in Th2 mediated disease. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T12:39:22Z (GMT). No. of bitstreams: 1 ntu-105-R03424009-1.pdf: 3078983 bytes, checksum: 02fa683153cfa459aed5f1358d80b0ed (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 中文摘要 iv
Abstract v Chapter 1 Introduction 1 1.1 Asthma 2 1.1.1 Immunology of asthma 2 1.1.2 CD4 T cell immune response 3 1.1.3 Type II immune response and allergy 3 1.1.4 Allergic asthma mediated by Th2 cells 4 1.1.5 Non-allergic asthma 5 1.1.6 Therapy for asthma 5 1.2 Mesenchymal stem cells (MSCs) 7 1.2.1 The immune regulation of MSCs 8 1.2.2 The interaction between MSCs and T cells 9 1.2.3 MSCs’ effect on helper T cells 9 1.2.4 Environmental effect on MSCs 10 1.2.5 The therapeutic role of MSCs 10 1.2.6 Placenta choriodecidual-membrane derived mesenchymal stem cells (pcMSCs) 12 1.3 MSCs and airway inflammation 13 Specific aim 14 Chapter 2 Materials and methods 15 2.1 Human peripheral blood mononuclear cells (PBMCs) separation 16 2.2 In vitro culture of PBMCs 16 2.3 Flow analysis 17 2.4 Cytokine measurement by Enzyme linked immunosorbent assay (ELISA) 17 2.5 Type 2 helper T cell (Th2) culture 17 2.6 Intracellular staining 18 2.7 RNA isolation 19 2.8 Detection of immunosuppressive gene by quantitative real-time polymerase chain reaction (qPCR) 19 2.9 Annexin V apoptosis assay 20 2.10 Transwell assay 20 2.11 Statistical analysis 20 Chapter 3 Results 22 3.1 pcMSCs are as effective as the common used bone marrow MSCs 23 3.2 pcMSCs suppress the function of Th2 cells 23 3.3 pcMSCs suppress T cell response from asthma patients 24 3.4 The cytokine production of T cells were suppressed by pcMSCs 24 3.5 CD4+ T cell immune response is reduced by pcMSCs 25 3.6 The suppression ability of Th2 response is equal between pcMSCs and bmMSCs 25 3.7 The immunosuppression of pcMSCs may not induce cell apoptosis 26 3.8 PD-1/PD-L1 signal may be enhanced during cocultuvation 26 3.9 The role of cell to cell contact is indeterminate 27 3.10 The immunosuppressive cytokine IL-10 is secreted by pcMSCs but may not be necessary for suppressing T cell function 27 3.11 pcMSCs may not be sensitive to the stimulation of Th2 cytokine IL-4 28 Chapter 4 Discussion 29 Chapter 5 Figures 37 Fig. 1 Examining the immunosuppressive function of pcMSCs 38 Fig. 2 Function of Th2 cells was suppressed by pcMSCs 39 Fig. 3 Immune responses of reactive T cell after cocultured with pcMSCs 40 Fig. 4 Suppression of cytokine production by pcMSCs 41 Fig. 5 Suppression of CD4+ T cell response by pcMSCs 42 Fig. 6 Comparison of the effects of pcMSCs and bmMSCs on IL-5 production 43 Fig. 7 Expression of Annexin V on T cell cocultured with pcMSCs 44 Fig. 8 PD-1 expression of T cells and PD-L1 expression of pcMSCs 45 Fig. 9 Suppressive function of pcMSCs when losing cell to cell contact 46 Fig. 10 The role of IL-10 in immunosuppression of pcMSCs 47 Fig. 11 IL-4’s effect on pcMSCs 48 Fig. 12 Conclusion 49 Reference 50 | |
| dc.language.iso | en | |
| dc.subject | 間葉幹細胞 | zh_TW |
| dc.subject | 過敏性氣喘 | zh_TW |
| dc.subject | 第二型輔助性T細胞 | zh_TW |
| dc.subject | 過敏性氣喘 | zh_TW |
| dc.subject | 間葉幹細胞 | zh_TW |
| dc.subject | 第二型輔助性T細胞 | zh_TW |
| dc.subject | Th2 cells | en |
| dc.subject | Th2 cells | en |
| dc.subject | allergic asthma | en |
| dc.subject | mesenchymal stem cells (MSCs) | en |
| dc.subject | allergic asthma | en |
| dc.subject | mesenchymal stem cells (MSCs) | en |
| dc.title | 探討mesenchymal stem cells對Th2細胞及過敏性疾病的調控 | zh_TW |
| dc.title | Study on the regulatory role of mesenchymal stem cells on Th2 cells and allergic diseases | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林泰元,周秀慧,陶秘華 | |
| dc.subject.keyword | 過敏性氣喘,間葉幹細胞,第二型輔助性T細胞, | zh_TW |
| dc.subject.keyword | allergic asthma,mesenchymal stem cells (MSCs),Th2 cells, | en |
| dc.relation.page | 59 | |
| dc.identifier.doi | 10.6342/NTU201601577 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-07-28 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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| ntu-105-1.pdf 未授權公開取用 | 3.01 MB | Adobe PDF |
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