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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 許秉寧(Ping-Ning Hsu) | |
dc.contributor.author | Yi-Lin Chen | en |
dc.contributor.author | 陳逸霖 | zh_TW |
dc.date.accessioned | 2021-06-13T06:10:22Z | - |
dc.date.available | 2014-10-05 | |
dc.date.copyright | 2011-10-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-07-25 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/34473 | - |
dc.description.abstract | Galectin-3是半乳糖苷結合凝集素的一種,具有廣泛的生物功能,參與在細胞的附著、活化、生長調控和凋亡。我們發現galectin-3可以引發T細胞表現FOXP3,這群由galectin-3所引起的FOXP3+ T細胞具有抑制性功能,能夠在共同培養的情形下抑制responder T細胞的活化增殖。另外,galectin-3在dextran sulfate sodium (DSS) 所引起的inflammatory bowel disease (IBD) 小鼠模式中也表現了其抑制性質,可以有效降低腸道發炎的症狀。我們以腹腔注射方法給予小鼠galectin-3,可以成功改善小鼠的腸道炎發病程度,而若是在galectin-3-/-小鼠上利用相同方式引發IBD,其發炎病狀會比野生型小鼠更加嚴重,這顯示了內生性galectin-3在腸道發炎反應的調控上也扮演著重要角色。接下來,我們進一步探討galectin-3的作用機制,藉由移植CD4+CD25- T細胞到免疫缺失小鼠體內以引發IBD的動物模式,我們發現經過galectin-3處理的CD4+CD25- T 細胞較不容易引起腸道炎,實驗結果顯示galectin-3可以作用在T細胞上,並且能調節CD4+CD25- T 細胞促進發炎的性質。另一方面,我們也利用施打anti-CD25單株抗體的方式去拮抗小鼠體內的調控性T細胞,以研究調控性T細胞是否參與在galectin-3的抑制性功能中。我們發現,一旦調控性T細胞被拮抗,galectin-3在DSS所引起的IBD小鼠模式裡就無法具有抑制發炎的效果,因此galectin-3的抑制性功能必須透過regulatory T 細胞才能發揮作用。以上實驗結果顯示著galectin-3能夠引發一群具有抑制性功能的FOXP3+ T細胞,從而調控腸道發炎反應。 | zh_TW |
dc.description.abstract | Galectin-3, a member of the β-galectoside-binding lectin family, exerts broad biological functions, involving in cell adhesion, cell activation, cell growth and apoptosis. We demonstrated that galectin-3 could induce FOXP3 expression in T cells and those FOXP3+ T cells induced by galectin-3 could supress T cell proliferation in vitro. In addition, galectin-3 could reduce inflammation in dextran sulfate sodium (DSS)–induced inflammatory bowel disease (IBD) mouse model. Treatment with soluble galectin-3 was able to ameliorate the severity of colitis in mice. On the other hand, galectin-3-/- mice demonstrated more severe inflammation in IBD model compared with wild type mice, suggesting that endogenous galectin-3 played an important role in regulation of intestinal inflammation. Moreover, we addressed the mechanism underlying the suppressive function of galectin-3 in vivo using another IBD mouse model which is induced by adoptive transfer with CD4+CD25- T cells into immunodeficient mice. Our results further demonstrated that galectin-3 could interact with T cells and reduce the severity of colitis induced by CD4+CD25- T cells. Furthermore, using anti-CD25 mAb to deplete Treg cells in vivo, we also found that the suppressive function of galectin-3 was mediated by regulatory T cells. In conclusion, these findings indicate that galectin-3 induces a population of FOXP3+ T cells with suppressive activity and involves in regulation of intestinal inflammation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T06:10:22Z (GMT). No. of bitstreams: 1 ntu-100-R98449006-1.pdf: 2903328 bytes, checksum: 890ad891ebebb67747eb403ad32232d8 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 謝辭 i
中文摘要 ii Abstract iii Chapter I. Introduction 1 The biological features of galectin-3 1 Functional properties of galecitn-3 2 The role of galectin-3 in inflammation 4 Galectins and regularoty T cells 5 Inflammatory bowel disease (IBD) and IBD mouse model 7 Chapter II. Aims and motivation of the study 9 Motivation 9 Aims 10 Chapter III. Materials and methods 12 Materials 12 1. Antibodies 12 2. Reagents 13 3. Buffer 16 Methods 17 1. Mice 17 2. Purification of recombinant human galectin-3 17 3. Isolation of human and mouse T cells 18 4. Culture of human and mouse T cells 19 5. Suppression assay 19 6. Flow cytometric analysis 20 6.1 Suface marker staining 20 6.2 Intracellular staining 21 7. IBD mouse model 21 7.1 DSS-induced colitis model 21 7.2 Adoptive transfer-induced colitis model 22 Chapter IV. Results 24 Galectin-3 induces FOXP3 expression in human T cells 24 FOXP3+ T cells induced by galectin-3 have suppressive function in vitro 25 Galectin-3 shows suppressive capacity in DSS-induced IBD mouse model 26 The absence of endogenous galectin-3 deteriorate the severity of IBD 28 Galectin-3 could interact with T cells and reduce the potential for IBD induced by CD25- T cells 29 The suppressive function of galectin-3 was mediated by regulatory T cells 31 Chapter V. Discussion 33 The dual role of galectin-3 in inflammatory diseases 33 The possible mechanism by which galectin-3 exerts suppressive function 35 The role of galectin-3 in IBD 37 Conclusion 38 References 40 Figure 1. Galectin-3 induces FOXP3 expression in human T cells in a dose-dependent manner. 50 Figure 2. Galectin-3-treated regulatory T cells retain the suppressive function in vitro 53 Figure 3. FOXP3+ T cells induced by galectin-3 have suppressive ability in vitro 56 Figure 4. Treatment of galectin-3 reduces the severity of colitis in DSS-induced IBD mouse model via induction of FOXP3+ regulatory T cells 59 Figure 5. Galectin-3-/- mice have more severe intestine inflammation in DSS-induced IBD mouse model 63 Figure 6. Galectin-3 could interact with T cells and reduce the inflammatory property of CD4+CD25- T cells 66 Figure 7. Galectin-3-induced amelioration of inflammation in IBD mouse model was mediated by regulatory T cells 70 | |
dc.language.iso | en | |
dc.title | Galectin-3藉由誘發調控性T細胞於小鼠模式中減緩腸道發炎性疾病 | zh_TW |
dc.title | Galectin-3 modulates inflammatory bowel disease in mouse model via induction of regulatory T cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 司徒惠康(Huey-Kang Sytwu),謝世良(Shie-Liang Hsieh) | |
dc.subject.keyword | 半乳糖凝集素蛋白,調控性T細胞,腸道發炎性疾病, | zh_TW |
dc.subject.keyword | galectin-3,Treg,IBD,DSS, | en |
dc.relation.page | 70 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-07-26 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 免疫學研究所 | zh_TW |
顯示於系所單位: | 免疫學研究所 |
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