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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 繆希椿 | |
| dc.contributor.author | Yu-Hua Hsu | en |
| dc.contributor.author | 許毓華 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:16:35Z | - |
| dc.date.available | 2022-09-08 | |
| dc.date.copyright | 2017-09-08 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-14 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66992 | - |
| dc.description.abstract | CREB (cAMP response element-binding protein) 結合蛋白(CBP)是一種轉錄共活化因子，可利用本身的組蛋白乙醯轉移酶(HAT)直接調控轉綠作用的進行，並且與多種蛋白有交互作用。當CBP產生突變在人類會造成魯賓斯坦-泰必氏綜合症(Rubinstein-Taybi syndrome, RTS)。在小鼠的胸腺細胞條件式剔除CBP，會有異常的胸腺發育，而且CD8細胞會表現出作用、記憶與先天性型態，並且在接受刺激後能大量快速產生伽瑪干擾素 (interferon-γ)。先前研究證實，CBP 胺基酸1382與1386位置 (老鼠為胺基酸1383與1387位置) 的絲氨酸會被進入細胞核的IKKα磷酸化而增進 CBP HAT的活性，而在此兩胺基酸位點突變的CBP較傾向與P53結合而不傾向與NF-κB結合。在突變CBP knock-in小鼠 (CBPS1383/1387Am/; AA 小鼠) 中，發現會有自發性腸炎的現象，並且其症狀與人類發炎性腸炎相似。因此我們假設在AA小鼠中，腸道發炎是由於異常的T細胞而造成的。在本研究中，我們證實AA小鼠的胸腺細胞數相對於野生型是較少的，但是在腸系膜淋巴結 (mLNs) 中，不論是CD4或是CD8 T細胞數都是上升的。在脾臟中與野生型相比，AA小鼠初始T細胞是顯著性下降且作用性T細胞是顯著性上升的。而在CD4與CD8 T細胞產生細胞激素的能力方面WT小鼠與AA小鼠是相似的，並且初始T細胞分化為TH1、TH2與TH17的能力也是沒有顯著性差異的。此外發炎型細胞激素與抗菌蛋白在AA小鼠大腸黏液層都是上升的，另外在DSS引起的腸道發炎模式中，AA小鼠的 mLNs 會有較多免疫細胞，並且將AA小鼠與WT小鼠混合飼養後，mLNs中的免疫細胞數目沒有顯著差異。 | zh_TW |
| dc.description.abstract | CREB (cAMP response element-binding protein) binding protein (CBP) is a transcriptional co-activator. It regulates transcription directly with its intrinsic histone acetyltransferase (HAT) domian. Mutation of CBP in human causes Rubinstein-Taybi syndrome (RTS), an autosomal-dominant disease. Moreover, T cell development in CBP conditional knock-out mice is abnormal. CBP deficient CD8 single-positive (SP) thymocytes possess an effector-, memory-, or innate-like T-cell phenotype and rapidly produce interferon-γ upon stimulation. Previous study indicated that nuclear IKKα phosphorylates CBP at Ser-1382 and Ser-1386 (mouse amino acids 1383 and 1387) and enhance CBP HAT activity. Mutant CBP was shown to switch binding preference from NF-κB to p53. Mutant CBP knock-in mice, CBPS1383/1387Am/m (AA) mice, were generated. They spontaneously develop colitis with features of human inflammatory bowel disease. Because CBP plays a crucial role in T cell development, we hypothesize that abnormal T cells cause chronic intestinal inflammation in the mutated CBP knock-in mice. In this study, the aim is to clarify the role of T cells in intestinal inflammation in AA mice. The results showed that the cell number of thymus was lower in AA mice than WT mice. However, T cells, including CD4 and CD8 T cells, were significantly increased in mesenteric lymph nodes (mLNs) of AA mice. Furthermore, naïve T cells were significantly decreased and effector T cells were significantly increased in AA mice. However, the cytokine-producing ability of T cells was similar in WT and AA mice and the serine phosphorylated CBP did not affect naïve CD4 T cells differentiate into TH1, TH2 and TH17 cells. Moreover, inflammatory cytokines and anti-microbial peptides (AMPs) were enhanced in colon mucus layer of AA mice. AA mice exhibited more immune cells in mLNs compared to WT mice after DSS treatment. In addition, AA mice had similar immune cell population in mLNs to WT mice according to DSS co-house study. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:16:35Z (GMT). No. of bitstreams: 1 ntu-106-R04449002-1.pdf: 5010979 bytes, checksum: fed9cb50243732c510bab5ddf098810a (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii Content v Figure of content viii I. Introduction 1 1. T cells 1 1.1. CD4 T cells 1 1.1.1. TH1 cells 1 1.1.2. TH2 cells 2 1.1.3. TH17 cells 2 1.2. CD8 T cells 3 2. CREB (cAMP response element-binding protein) binding protein (CBP) 3 2.1. CBP and disease 4 2.2. CBP and T cell 5 2.3. CBP and NF-κB crosslink to immune 6 3. Inflammatory bowel diseases (IBDs) 7 3.1. TH1 cell-associated colitis 7 3.2. TH2 cell-associated colitis 7 3.3. TH17 cell-associated colitis 8 3.4. IL-22 8 4. Significance and Specific aim 9 II. Materials and Methods 11 1. Materials 11 1.1. Mice 11 1.2. Antibodies and cytokines 11 1.3. Buffers 13 1.4. Chemicals and Reagents 14 1.5. Primers 15 2. Methods 18 2.1. Cell sorting 18 2.2. In vitro T cells culture 18 2.2.1. In vitro CD4 T cells culture 18 2.2.2. In vitro CD8 T cells culture 19 2.2.3. In vitro T helper differentiation 20 2.3. Quantitative real-time PCR 21 2.4. ELISA 21 2.5. DSS-induced colitis model 22 III. Result 23 1. Abnormal thymus development in CBPS1383/1387Am/m (AA) mice. 23 2. Population of T cell in spleen, pLNs and mLNs 24 3. Comparable cytokine production by T cell in AA mice and WT mice is comparable. 25 4. An ability of T helper cells differentiated into TH1, TH2 and TH17 cells is comparable between AA and WT mice. 26 5. Elevated inflammatory cytokine and anti-microbial peptides, and normal amount of mucins mRNA transcript in mucus layer of AA mice 27 6. Population of immune cell in mLNs is increased in AA mice compared to WT mice after DSS treatment. 29 7. Comparable immune cell population in mLNs of cohoused AA mice and WT mice after DSS treatment. 31 8. TH17 cell related responses in 8 weeks old AA mice 32 IV. Discussion and conclusion 33 V. Figure 40 VI. References 60 VII. Supplementary 66 | |
| dc.language.iso | en | |
| dc.subject | CREB結合蛋白 | zh_TW |
| dc.subject | T 細胞 | zh_TW |
| dc.subject | 腸炎 | zh_TW |
| dc.subject | colitis | en |
| dc.subject | CBP | en |
| dc.subject | T cell | en |
| dc.subject | IBD | en |
| dc.title | 在CBPS1383/1387Am/m 小鼠腸道發炎反應之T細胞分析 | zh_TW |
| dc.title | Profiling T cells in intestinal inflammation CBPS1383/1387Am/m mice | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 伍安怡,張雅貞,陳青周 | |
| dc.subject.keyword | CREB結合蛋白,T 細胞,腸炎, | zh_TW |
| dc.subject.keyword | CBP,T cell,colitis,IBD, | en |
| dc.relation.page | 67 | |
| dc.identifier.doi | 10.6342/NTU201702139 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-14 | |
| 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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