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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 莊雅惠(Ya-Hui Chuang) | |
| dc.contributor.author | Yu-Hsin Hsueh | en |
| dc.contributor.author | 薛郁馨 | zh_TW |
| dc.date.accessioned | 2021-06-16T06:34:23Z | - |
| dc.date.available | 2024-08-04 | |
| dc.date.copyright | 2014-10-09 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-04 | |
| dc.identifier.citation | 1. Hofmann, S.R., et al., Biological properties and regulation of IL-10 related cytokines and their contribution to autoimmune disease and tissue injury. Clin Immunol, 2012. 143(2): p. 116-27.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57080 | - |
| dc.description.abstract | IL-10 family cytokine對於保護組織、避免組織因為感染及發炎反應而受到破壞相當重要。其中IL-10可抑制發炎反應並且也可抑制肝纖維化的發生。而IL-22則是對於上皮組織的平衡、修復以及傷口癒合相當重要。目前的研究顯示IL-10及IL-22在免疫反應的調控上皆扮演了重要的角色，特別是在肝臟的發炎反應中，兩者皆可有效的減緩肝臟的發炎反應。IL-10及IL-22對於許多不同的自體免疫疾病亦有抑制的效果。原發性膽道硬化症 (Primary Biliary Cirrhosis，PBC) 為一種因免疫反應引起肝內小膽管的發炎及損壞的肝臟自體免疫疾病，導致慢性膽汁鬱積，最終會造成肝纖維化與肝硬化。本研究探討IL-10及IL-22對於肝臟自體免疫疾病 PBC的影響。由於AAV (adeno-associated virus)僅會引起輕微的發炎反應，且可長久的表達其所攜帶的基因，因此可作為良好的載體。我們利用攜帶IL-10及IL-22基因的AAV以尾靜脈注射方式打入以2-OA-OVA/α-GalCer致敏的PBC小鼠體內，觀察PBC小鼠的自體抗體、肝臟單核細胞浸潤及病理變化。我們發現給予IL-10的PBC小鼠肝臟中的B cells數量下降、Foxp3+ CD4 T cells的數量上升，肝臟中的granulomas數目及MMP-9的表現降低。而給予IL-22的PBC小鼠肝臟單核細胞數顯著下降，尤其是T cells及B cells。IL-10 也許可透過降低B cells的數目及增加肝臟中Tregs的數量以減緩PBC的發炎反應，或透過降低granulomas的形成及減少MMP-9的表現以抑制fibrosis。而IL-22則可減緩PBC所引起的肝臟發炎細胞浸潤，特別是T cells及B cells。因此IL-10及IL-22均會降低肝臟自體免疫疾病PBC的發炎反應。 | zh_TW |
| dc.description.abstract | IL-10 family cytokines are essential for the prevention of tissue damage caused by excessive inflammatory responses as well as maintaining the homeostasis of tissue epithelial layers. IL-10 is an anti-inflammatory and anti-fibrotic cytokine. IL-22 preserves tissue integrity with enhanced wound-healing and tissue repair activities. Both IL-10 and IL-22 are important in controlling the inflammatory response, especially in hepatitis. In addition IL-10 and IL-22 also have the protective effects in the variety of autoimmune diseases. Primary biliary cirrhosis (PBC) is a liver autoimmune disease, characterized by the immune mediated infiltration and destruction of the bile duct, which leads to cholestasis, fibrosis, and finally, cirrhosis. Our specific aim is to investigate the effects of IL-10 and IL-22 on the regulation of PBC. Because of the minute immune response and the long-term expression of the gene, adeno-associated virus (AAV) is a good vector for gene transfer. In this study, mouse IL-10 and IL-22 expressing AAV were injected to 2-OA-OVA/α-GC immunized mice and PBC features including serum anti-mitochondrial antibodies (AMA) titer, liver mononuclear cells infiltration and the histopathology in these cytokine expressed mice were then examined. Our results showed that administration of IL-10 decreased B cells but increased Foxp3+ CD4 T cells in the liver of 2-OA-OVA/α-GC immunized PBC mice. Moreover, reduced granulomas and MMP-9 expression were observed in the liver of IL-10 injected PBC mice. IL-22 administration reduced the liver mononuclear cells, especially T cells and B cells in 2-OA-OVA/α-GC immunized PBC mice. These results suggested that IL-10 in PBC might inhibit liver inflammation by decreasing B cells and increasing Foxp3+ regulatory T cells. In addition, IL-10 may suppress liver fibrosis by reducing the granulomas formation and MMP-9 expression. IL-22 could ameliorate liver inflammation by decreasing T cell and B cell infiltration in PBC mice. Taken together, our study demonstrated the down-regulatory effects of IL-10 and IL-22 on PBC. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T06:34:23Z (GMT). No. of bitstreams: 1 ntu-103-R01424001-1.pdf: 2815543 bytes, checksum: 38fed62bb609e0501134bd7556e49a57 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 致謝 i
摘要 ii Abstract iii 縮寫對照表 v 目錄 vi 圖目錄 ix 第一章 研究背景 1 1.1 IL-10家族之細胞激素 (IL-10 Family Cytokine) 1 1.1.1 IL-10及其訊號傳遞 1 1.1.2 IL-10之分泌細胞及作用細胞 2 1.1.3 IL-10之生理功能 2 1.1.4 IL-10在發炎反應及自體免疫疾病中的角色 2 1.1.5 IL-10對於肝臟的保護作用 3 1.1.6 IL-22及其訊號傳遞 4 1.1.7 IL-22之分泌細胞及作用細胞 4 1.1.8 IL-22之生理功能 4 1.1.9 IL-22在發炎反應及自體免疫疾病中的角色 5 1.1.10 IL-22對於肝臟的保護作用 5 1.2 Adeno-associated virus (AAV) 6 1.2.1 AAV之基因及其功能 6 1.2.2 AAV作為基因表現之載體 6 1.2.3 AAV所引起的免疫反應 7 1.3 肝臟及其免疫系統 7 1.3.1 原發性膽道硬化症 (Primary Biliary Cirrhosis，PBC) 8 1.3.2 PBC的致病機轉 8 1.3.3 PBC之免疫反應 9 1.3.4 2-OA-induced PBC小鼠動物模式 10 1.4 研究目的 10 第二章 實驗材料與方法 11 2.1製備帶有IL-10及IL-22之pAAV-IRES-GFP 11 2.2 3H-Thymidine incorporation assay 11 2.3西方墨點法 (Western blotting assay) 12 2.4 AAV組裝 (cotransfection pAAV-IRES-GFP、pAAV-DJ及pHelper) 12 2.5 AAV純化 13 2.6 AAV濃縮及定量 13 2.7 Polymerase Chain Reaction (PCR) 13 2.8 實驗用小鼠 14 2.9 AAV注射及PBC小鼠模式 14 2.10 血清樣本收集 15 2.11 小鼠肝臟灌流與病理切片製作 15 2.12 小鼠肝臟單核細胞的純化 15 2.13 流式細胞儀 (flow cytometry)分析細胞表面抗原 15 2.14 以ELISA測定PBC小鼠血清中的anti-mPDC-E2 IgM及IgG 16 2.15 以ELISA測定血清中的細胞激素 17 2.16 組織及細胞RNA之萃取 17 2.17 RNA反轉錄成cDNA 18 2.18 以即時定量反轉錄聚合酶連鎖反應偵測特定基因之mRNA表現 18 2.19 Granulomas之分析及計算 19 2.20 繪圖與統計分析 19 第三章 實驗結果 20 3.1 製備pAAV-mIL-10及pAAV-mIL-22並確認其功能 20 3.2 AAV以尾靜脈注射的方式打入小鼠，其所攜帶之細胞激素可在小鼠肝臟表現至少10週 20 3.3 當PBC小鼠體內表現高量之IL-10時，肝臟B cells數量下降但CD4 T cells及Foxp3+ CD4 T cells數目升高 21 3.4 當PBC小鼠體內表現高量之IL-10時，可減少肝臟granulomas的形成及纖維化相關基因的表現 22 3.5 當PBC小鼠體內表現較高的IL-22時，可發現肝臟單核細胞數、B cells數以及T cells數量皆降低 23 3.6 當PBC小鼠體內表現高量之IL-22時，可減少肝臟中較大的granulomas的形成 24 第四章 討論 25 圖 31 參考文獻 55 附錄 64 | |
| dc.language.iso | zh-TW | |
| dc.subject | 原發性膽道硬化症 | zh_TW |
| dc.subject | IL-10 | zh_TW |
| dc.subject | IL-22 | zh_TW |
| dc.subject | AAV | zh_TW |
| dc.subject | 自體免疫疾病 | zh_TW |
| dc.subject | IL-22 | en |
| dc.subject | IL-10 | en |
| dc.subject | AAV | en |
| dc.subject | autoimmune disease | en |
| dc.subject | primary biliary cirrhosis | en |
| dc.title | 探討Interleukin-10及Interleukin-22於原發性膽道硬化症的免疫調節作用 | zh_TW |
| dc.title | Study on the Immunoregulatory Effects of Interleukin-10 and Interleukin-22 on Primary Biliary Cirrhosis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 胡忠怡(Chung-Yi Hu),孫昭玲(Jau-Ling Suen) | |
| dc.subject.keyword | IL-10,IL-22,原發性膽道硬化症,自體免疫疾病,AAV, | zh_TW |
| dc.subject.keyword | IL-10,IL-22,primary biliary cirrhosis,autoimmune disease,AAV, | en |
| dc.relation.page | 68 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-08-04 | |
| 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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