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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 繆希椿 | |
| dc.contributor.author | Shin-Ying Lin | en |
| dc.contributor.author | 林欣穎 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:53:30Z | - |
| dc.date.available | 2016-10-05 | |
| dc.date.copyright | 2011-10-05 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-18 | |
| dc.identifier.citation | References
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46086 | - |
| dc.description.abstract | 轉錄因子c-Maf在第二型輔助T淋巴球(Th2)中特別調控介白素4 (IL-4)，最近的研究指出c-Maf亦能分別在第十七型輔助T淋巴球(Th17)中調控介白素21 (IL-21)及在第一型調節性T淋巴球 (type 1 regulatory T cell) 中調控介白素10 (IL-10)的表現，然而對於c-Maf的磷酸化如何調控介白素的相關研究尚未清楚。根據實驗室之前的實驗結果，發現活體外c-Maf的磷酸化可以調節IL-4的表現，而且c-Maf被磷酸化的位點也被界定。因此，在我的研究，從小鼠分離出primary CD4 T細胞，並大量表現野生型(WT)或是無法磷酸化的c-Maf，進而利用染色質沉澱技術(chromatin immunoprecipitation analysis) 探討在c-Maf的酪胺酸磷酸化的有無是否會改變結合到DNA的能力，進而影響IL-4及IL-21的表現量。結果發現酪胺酸能被磷酸化的WT c-Maf相較於不具有酪胺酸磷酸化能力的突變型c-Maf對於Il4 啟動子有較強的DNA結合能力，然而對於Il21啟動子則沒有影響。造成在這兩者不同影響的機制則是需要進一步的研究。 | zh_TW |
| dc.description.abstract | c-Maf, is known as a Th2 specific transcription factor that could transactivate IL-4 gene expression. Recent studies have shown that c-Maf could transactivate Il21 and Il10 in Th17 cells and type 1 regulatory T cells (Tr1), respectively. However, the function of the tyrosine phosphorylated c-Maf remains unknown. Previous studies in our lab have shown that the phosphorylation of c-Maf could regulate the IL-4 production in vitro. Furthermore, the tyrosine residues of c-Maf could be phosphorylated have been identified. Thus, in my research, I study whether the tyrosine phosphorylated c-Maf could affect the IL-4 and IL-21 production through its DNA binding to the respective promoters. The binding abilities of Il4 and Il21 promoters by tyrosine-phospho-deficient c-Maf and WT c-Maf in primary T cells were analyzed by chromatin immunoprecipitation (ChIP) analysis. The results demonstrated that the tyrosine phosphorylation of c-Maf could enhance its DNA binding to the Il4, but not Il21, promoters in vivo. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:53:30Z (GMT). No. of bitstreams: 1 ntu-100-R98449008-1.pdf: 1334581 bytes, checksum: 9aa140b1f2e2c327bea3d36fbee86344 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 目錄
致謝 I 中文摘要 II Abstract III Chapter 1. Introduction 1 1.1 CD4+ T cells 1 1.1.1 The differentiation of Th2 cells 1 1.1.2 The differentiation of Th17 cells 2 1.1.3 The differentiation of type 1 regulatory T (Tr1) cells 3 1.2 An overview of c-Maf 4 1.3 c-Maf: a transcription factor of IL-4, IL-21 and IL-10 5 1.4 Rationale 7 Chapter 2. Experimental Procedure 9 2.1 Construction 9 2.2 Cell culture and transfection 9 2.3 Western blotting 10 2.4 In vitro T helper cell differentiation 10 2.5 Production of retrovirus 10 2.6 Retroviral transduction 11 2.7 Chromatin immunoprecipitation assay 11 2.8 Quantitative PCR analysis 13 2.9 Statistical analysis 13 Chapter 3. Experimental Materials 14 3.1 Mice 14 3.2 Chemicals and reagents 14 3.3 Enzymes, cytokines and antibodies 16 3.4 Kits 17 3.5 Medium, solutions and buffers 18 Chapter 4. Results 23 1. The phosphorylation of c-Maf enhances the IL-4 production through DNA binding in primary T cells. 23 1.1 Y345F c-Maf is not an appropriate control in ChIP analysis because of its lower protein expression. 24 1.2 Y341F c-Maf was used as a control in the ChIP experiment. 25 2. The phosphorylation of c-Maf could not influence the IL-21 production through DNA binding ability in T cells. 25 Chapter 5. Discussion 27 1. Y345F c-Maf has lower DNA binding ability to Il4 promoter because of its lower protein expression. 27 2. We generated RFP RV-Tec construct to perform co-transduction experiment and further determine whether the phoshpohrylation of c-Maf could influence the recruitment its mediated genes. 28 3. The tyrosine phosphorylated c-Maf may regulate Il21 through other mechanisms. 29 4. The tyrosine phosphorylation of c-Maf may influence the recruitment to Il10 and Il21 promoters in Tr1 cells. 30 References 32 Figures 37 Figure 1. The diagram of the experimental design. 38 Figure 2. The transduction efficiency of primary CD4+ T cells at day 4. 40 Figure 3. The phosphorylation of c-Maf affects IL-4 production through DNA binding ability in vivo. 42 Figure 4. Construction and expression of GFP RV Y341F c-Maf. 44 Figure 5. The transduction efficiency in primary CD4+ T cells was determined by flow cytometry. 46 Figure 6. The phosphorylation of c-Maf affects IL-4 production through DNA binding ability in primary CD4+ T cells. 48 Figure 7. The transduction efficiency in primary CD4+ T cells was determined by flow cytometry. 50 Figure 9. Construction and expression of RFP RV Tec . 54 | |
| dc.language.iso | en | |
| dc.subject | 介白素21 | zh_TW |
| dc.subject | T淋巴細胞 | zh_TW |
| dc.subject | c-Maf | zh_TW |
| dc.subject | 磷酸化 | zh_TW |
| dc.subject | 介白素4 | zh_TW |
| dc.subject | phosphorylation | en |
| dc.subject | IL-21 | en |
| dc.subject | IL-4 | en |
| dc.subject | T cell | en |
| dc.subject | c-Maf | en |
| dc.title | 探討在T淋巴細胞中酪胺酸磷酸化之c-Maf對於細胞激素基因的結合機轉 | zh_TW |
| dc.title | Recruitment of tyrosine-phosphorylated c-Maf to
c-Maf mediated cytokine genes in T cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 司徒惠康,賴明宗 | |
| dc.subject.keyword | T淋巴細胞,c-Maf,磷酸化,介白素4,介白素21, | zh_TW |
| dc.subject.keyword | T cell,c-Maf,phosphorylation,IL-4,IL-21, | en |
| dc.relation.page | 54 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-18 | |
| 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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