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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許輔(Fuu Sheu) | |
| dc.contributor.author | Pei-Hua Wu | en |
| dc.contributor.author | 巫沛樺 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:48:07Z | - |
| dc.date.available | 2018-08-24 | |
| dc.date.copyright | 2016-08-24 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-12 | |
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J., Chuang, W. I., & Sheu, F. (2010). Polysaccharides PS-G and protein LZ-8 from Reishi (Ganoderma lucidum) exhibit diverse functions in regulating murine macrophages and T lymphocytes. Journal of agricultural and food chemistry, 58(15), 8535-8544. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49783 | - |
| dc.description.abstract | 金針菇 (Flammulina velutipes) 為常見的食用菇菌之一，也被證明具有多種保健功效。FIP-fve為從金針菇分離出的免疫調節蛋白。文獻指出FIP-fve具有活化小鼠脾細胞、巨噬細胞及外周血單核球細胞等多種免疫細胞之能力，但目前尚無針對樹突細胞之相關研究。本研究之目的為探討FIP-fve是否能夠活化小鼠樹突細胞並調節T細胞免疫反應，以及探討FIP-fve作為樹突細胞疫苗佐劑之潛力。
首先，體外試驗中發現 FIP-fve 可以刺激小鼠骨髓衍生性樹突細胞 (bone marrow-derived dendritic cells, BMDCs) 表現 CD40、CD80、CD86 及 MHC (major histocompatibility complex) class II，且能誘導樹突細胞產生 TNF-α, IL-1β, IL-6 , IL-12及IL-10 等細胞激素，在 TLR4 缺陷小鼠中則發現 FIP-fve 刺激樹突細胞之效果明顯受到抑制，證明其活化路徑很可能是透過細胞表面之 TLR4 受體。另一方面，研究發現 FIP-fve 需要透過抗原呈獻細胞來活化 T 細胞，在 T 細胞與樹突細胞同時存在下，FIP-fve 可使T細胞產生大量 IFN-γ，且能使T細胞之活化分子標誌 CD25 及 CD69 表現量上升。利用對 OVA 具特異性之 DO11.10 小鼠的 CD4+ T 細胞與經過FIP-fve活化之樹突細胞共同培養，發現經FIP-fve活化之樹突細胞可以增強 OVA 特異性 CD4+ T 細胞增生，且能使 T 細胞產生 TH1 免疫反應。在體內試驗的部分發現以FIP-fve 與 OVA 刺激之樹突細胞作為疫苗免疫小鼠，可以誘發小鼠體內產生 OVA特異性免疫反應，另外在 MO5 黑色素瘤小鼠模式中，以 FIP-fve 作為佐劑可以增強罹癌小鼠產生抗腫瘤免疫反應以抑制腫瘤生長。藉由上述結果證明FIP-fve 活化之樹突細胞能夠調節 TH1 細胞分化，增強抗原特異性 T 細胞免疫反應，且作為樹突細胞疫苗佐劑可以增強疫苗的抗腫瘤效果。 | zh_TW |
| dc.description.abstract | Golden needle mushroom (Flammulina velutipes) is one of the most common edible mushrooms and has been demonstrated to have many health benefits. FIP-fve is an immunomodulatory protein isolated from F. velutipes and was proved to have an ability to activate many immunocytes such as murine splenocytes, macrophages and hPBMCs. The aim of this study was to demonstrate whether FIP-fve could activate murine dendritic cells and further regulate T cell immune responses, and to investigate its activity as a vaccine adjuvant.
The results indicated that FIP-fve could up-regulate surface marker expression of CD40, CD80, CD86, and MHC calss II, and induce cytokines production of TNF-α, IL-1β, IL-6, IL-12, and IL-10 by BMDCs in vitro. We then found that the ability of FIP-fve to activate DCs was remarkably limited in TLR4 knock out mice. These results demonstrated that FIP-fve activated murine DCs mainly through the TLR4 pathway. Furthermore, FIP-fve needed the presence of antigen-presenting cells (APCs) to activate T cell. In the presence of DCs, FIP-fve could induce great amount IFN-γ production and up-regulate the expression of CD25 and CD69 by T cells. Moreover, we isolated CD4+ T cell from OVA-specific DO11.10 mice and cultured with OVA pulsed FVE-treated DCs and OVA antigen. Our data showed that FVE-treated DCs enhanced OVA-specific CD4+ T cell proliferation and IFN-γ production, and demonstrated that FIP-fve could induce TH1 response. On the other hand, we used FIP-fve as a vaccine adjuvant, and found that FIP-fve could induce OVA-specific immune response in vivo. Immunization of mice with OVA pulsed FVE-treated DCs induced antitumor response in a murine MO5 melanoma model and suppressed the tumor growth. According to these findings, we demonstrated that FIP-fve could regulate TH1 cell differentiation through DC maturation and boost antigen-specific immune responses, and enhanced the effect of antitumor response by acting as a dendritic cell vaccine adjuvant. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:48:07Z (GMT). No. of bitstreams: 1 ntu-105-R03628208-1.pdf: 3931351 bytes, checksum: 5ade2a65b04e3acd53547e18a7d3b609 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 口試委員會審定書 I
致謝 II 摘要 IV Abstract V 目錄 VII 圖目錄............................................................... X 縮寫對照表 XI 第一章 前言 1 第一節 金針菇介紹 1 1.1. 金針菇簡介 1 1.2. 金針菇之成分 1 1.3. 金針菇之生物活性 2 第二節 金針菇免疫調節蛋白FIP-fve 2 2.1. 金針菇免疫調節蛋白FIP-fve簡介 2 2.2. FIP-fve之免疫調節活性 3 2.3. FIP-fve之安定性 5 第三節 樹突細胞 6 3.1. 樹突細胞簡介 6 3.2. 樹突細胞之功能 7 3.3. 樹突細胞之活化與成熟 7 3.4. 樹突細胞與 T 細胞之交互作用 8 第四節 T細胞免疫反應 9 4.1. T細胞簡介 9 4.2. TH1 與 TH2 之免疫反應 9 4.3. 癌症與T細胞免疫反應 10 第五節 腫瘤免疫治療 11 5.1. 腫瘤免疫治療簡介 11 5.2. 樹突細胞疫苗與疫苗佐劑 11 第六節 研究動機與目的 12 第二章 材料與方法 14 第一節 金針菇免疫調節蛋白 FIP-fve之純化與鑑定 14 1.1. FIP-fve之純化 14 1.2. SDS-PAGE 膠體電泳分析 16 第二節 FIP-fve活化小鼠骨髓衍生性樹突細胞之免疫活性 18 第三節 FIP-fve活化小鼠脾細胞之免疫活性 22 第四節 FIP-fve刺激小鼠 CD90.2+ T 細胞之免疫活性 26 第五節 FIP-fve 刺激之樹突細胞活化 OVA 特異性 T 細胞免疫反應 30 第六節 FIP-fve 之佐劑活性試驗 33 第七節 MO5腫瘤小鼠模式試驗 36 第八節 統計分析 38 第三章 結果 39 第一節 FIP-fve之純化 39 第二節 FIP-fve活化小鼠骨髓衍生性樹突細胞 39 2.1. FIP-fve誘導樹突細胞分泌細胞激素 39 2.2. FIP-fve 刺激樹突細胞表現表面分子 40 2.3. FIP-fve透過TLR4路徑活化小鼠樹突細胞 40 第三節 FIP-fve 活化非特異性免疫反應 41 3.1. FIP-fve 活化小鼠脾細胞 41 3.2. FIP-fve 刺激小鼠脾細胞中之 T 細胞表現 CD69 及 CD25 41 3.3. FIP-fve 無法直接活化 CD90.2 T 細胞 42 3.4. FIP-fve需透過抗原呈獻細胞活化T細胞 42 第四節 FIP-fve活化特異性免疫反應 43 4.1. FIP-fve 刺激之 DCs 促進 OVA 特異性 T 細胞活化 43 4.2. FIP-fve 無法直接刺激 DO11.10 CD4+ T 細胞 43 第五節 FIP-fve作為疫苗佐劑之活性 44 5.1. FIP-fve 作為佐劑活化 OVA 特異性免疫反應 44 5.2. FIP-fve 作為佐劑活化 MO5 腫瘤特異性免疫反應 44 第六節 在 MO5 小鼠模式中 FIP-fve 作為佐劑之抗腫瘤效果 45 第四章 討論 47 第一節 FIP-fve活化小鼠骨髓衍生性樹突細胞 47 第二節 FIP-fve活化非特異性T細胞免疫反應 49 第三節 FIP-fve需透過抗原呈獻細胞活化T細胞 50 第四節 FIP-fve活化抗原特異性免疫反應 50 第五節 以FIP-fve作為樹突細胞疫苗佐劑之活性 51 第六節 在MO5腫瘤小鼠模式中FIP-fve增強抗腫瘤效果 52 第五章 結論 54 第六章 參考文獻 55 附圖................................................................66 | |
| dc.language.iso | zh-TW | |
| dc.subject | 疫苗佐劑 | zh_TW |
| dc.subject | 金針菇 | zh_TW |
| dc.subject | 樹突細胞疫苗 | zh_TW |
| dc.subject | 骨髓衍生性樹突細胞 | zh_TW |
| dc.subject | 免疫調節蛋白 | zh_TW |
| dc.subject | vaccine adjuvant | en |
| dc.subject | Flammulina velutipes | en |
| dc.subject | dendritic cell vaccine | en |
| dc.subject | immunomodulatory protein | en |
| dc.subject | bone marrow-derived dendritic cells | en |
| dc.title | 金針菇免疫調節蛋白FIP-fve活化小鼠樹突細胞調節T細胞免疫反應及作為腫瘤疫苗佐劑之活性 | zh_TW |
| dc.title | Immunomodulatory Protein FIP-fve of Flammulina velutipes Activates Murine Dendritic Cells to Regulate T Cell Immune Responses and Acts as a Cancer Vaccine Adjuvant | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 周志輝(Chi-Fai Chau),潘敏雄(Min-Hsiung Pan),繆希椿(Shi-Chuen Miaw) | |
| dc.subject.keyword | 金針菇,免疫調節蛋白,骨髓衍生性樹突細胞,樹突細胞疫苗,疫苗佐劑, | zh_TW |
| dc.subject.keyword | Flammulina velutipes,immunomodulatory protein,bone marrow-derived dendritic cells,dendritic cell vaccine,vaccine adjuvant, | en |
| dc.relation.page | 88 | |
| dc.identifier.doi | 10.6342/NTU201602333 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-12 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 園藝暨景觀學系 | zh_TW |
| 顯示於系所單位： | 園藝暨景觀學系 | |
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