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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 朱清良(Ching-Liang Chu) | |
| dc.contributor.author | Yi-Chun Sung | en |
| dc.contributor.author | 宋怡君 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:25:08Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-18 | |
| dc.identifier.citation | 1 Kino, K. et al. Isolation and characterization of a new immunomodulatory protein, ling zhi-8 (LZ-8), from Ganoderma lucidium. The Journal of biological chemistry 264, 472-478 (1989).
2 Tanaka, S. et al. Complete amino acid sequence of an immunomodulatory protein, ling zhi-8 (LZ-8). An immunomodulator from a fungus, Ganoderma lucidium, having similarity to immunoglobulin variable regions. The Journal of biological chemistry 264, 16372-16377 (1989). 3 Huang, L. et al. Crystal structure of LZ-8 from the medicinal fungus Ganoderma lucidium. Proteins 75, 524-527, doi:10.1002/prot.22346 (2009). 4 Chu, C. L., Chen Dz, C. & Lin, C. C. A novel adjuvant Ling Zhi-8 for cancer DNA vaccines. Human vaccines 7, 1161-1164, doi:10.4161/hv.7.11.17753 (2011). 5 Kino, K. et al. Immunomodulator, LZ-8, prevents antibody production in mice. International journal of immunopharmacology 13, 1109-1115 (1991). 6 Haak-Frendscho, M., Kino, K., Sone, T. & Jardieu, P. Ling Zhi-8: a novel T cell mitogen induces cytokine production and upregulation of ICAM-1 expression. Cell Immunol 150, 101-113, doi:10.1006/cimm.1993.1182 (1993). 7 Hsu, H. Y. et al. Reishi Protein LZ-8 Induces FOXP3(+) Treg Expansion via a CD45-Dependent Signaling Pathway and Alleviates Acute Intestinal Inflammation in Mice. Evidence-based complementary and alternative medicine : eCAM 2013, 513542, doi:10.1155/2013/513542 (2013). 8 Yeh, C. H., Chen, H. C., Yang, J. J., Chuang, W. I. & Sheu, F. 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, 8535-8544, doi:10.1021/jf100914m (2010). 9 Rescigno, M. Dendritic cell-epithelial cell crosstalk in the gut. Immunological reviews 260, 118-128, doi:10.1111/imr.12181 (2014). 10 Coombes, J. L. & Powrie, F. Dendritic cells in intestinal immune regulation. Nature reviews. Immunology 8, 435-446, doi:10.1038/nri2335 (2008). 11 Coombes, J. L. et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. The Journal of experimental medicine 204, 1757-1764, doi:10.1084/jem.20070590 (2007). 12 Mills, K. H. Regulatory T cells: friend or foe in immunity to infection? Nature reviews. Immunology 4, 841-855, doi:10.1038/nri1485 (2004). 13 von Herrath, M. G. & Harrison, L. C. Antigen-induced regulatory T cells in autoimmunity. Nature reviews. Immunology 3, 223-232, doi:10.1038/nri1029 (2003). 14 Kretschmer, K. et al. Inducing and expanding regulatory T cell populations by foreign antigen. Nature immunology 6, 1219-1227, doi:10.1038/ni1265 (2005). 15 Kim, J. J., Shajib, M. S., Manocha, M. M. & Khan, W. I. Investigating intestinal inflammation in DSS-induced model of IBD. Journal of visualized experiments : JoVE, doi:10.3791/3678 (2012). 16 Liu, H., Hu, B., Xu, D. & Liew, F. Y. CD4+CD25+ regulatory T cells cure murine colitis: the role of IL-10, TGF-beta, and CTLA4. Journal of immunology (Baltimore, Md. : 1950) 171, 5012-5017 (2003). 17 Mottet, C., Uhlig, H. H. & Powrie, F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 170, 3939-3943 (2003). 18 Peterson, L. W. & Artis, D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nature reviews. Immunology 14, 141-153, doi:10.1038/nri3608 (2014). 19 Artis, D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nature reviews. Immunology 8, 411-420, doi:10.1038/nri2316 (2008). 20 McDole, J. R. et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483, 345-349, doi:10.1038/nature10863 (2012). 21 Iwata, M. et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21, 527-538, doi:10.1016/j.immuni.2004.08.011 (2004). 22 Vicente-Suarez, I. et al. Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells. Mucosal immunology 8, 141-151, doi:10.1038/mi.2014.51 (2015). 23 Fantini, M. C., Dominitzki, S., Rizzo, A., Neurath, M. F. & Becker, C. In vitro generation of CD4+ CD25+ regulatory cells from murine naive T cells. Nature protocols 2, 1789-1794, doi:10.1038/nprot.2007.258 (2007). 24 Cardona, S. et al. Storage conditions of intestinal microbiota matter in metagenomic analysis. BMC microbiology 12, 158, doi:10.1186/1471-2180-12-158 (2012). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49358 | - |
| dc.description.abstract | LZ-8 (Ling-Zhi 8)是屬於蕈菇類免疫調節蛋白(Fungal immunomodulatory protein, FIP)的一種，由日本學者Kino博士從靈芝 (Ganoderma lucidium) 菌絲體 (mycelia) 分離純化出來的小分子蛋白，分子量大約為12.4kD，其構造與人類免疫球蛋白重鏈區之可變區域的胺基酸序列及二級結構有高度的相似性。根據目前研究報告顯示，LZ-8具備有抗過敏、抗發炎、降低移植排斥等效果；同時，LZ-8也被發現有刺激免疫細胞引發免疫反應之能力，例如提升清除及抑制腫瘤細胞蔓延的效果等，故能定義LZ-8為免疫調節蛋白。由先前餵食小鼠LZ-8的初步實驗結果發現，小鼠體內的CD25+ FOXP3+調節性T細胞比例在脾臟以及腸隙膜淋巴結有顯著的增加，而這其中的機制仍是未知的；由前人文獻指出，腸道中FOXP3+ 調節性T細胞的產生，與A酸(Retinoic acid)增強CD11c+ CD103+ 調節性樹突細胞抗原呈現功能有關，由我們添加LZ-8於體外培養的調節性樹突細胞實驗結果得到，LZ-8能顯著提升此細胞的乙醛脫氫酶 (Aldehyde dehydrogenase1 family1, member 2, ALDH1A2) 訊息核醣核酸 (messenger ribonucleic acid, mRNA)的表現，將LZ-8培養後的調節性樹突細胞與T細胞共培養後能使FOP3+ 調節性T細胞生成比例提升，在小鼠腸炎模式的實驗中，在引發腸炎之前和引發腸炎過程中持續餵食小鼠LZ-8能夠顯著減緩小鼠腸炎的症狀。綜合以上體內與體外的初步結果，顯示口服LZ-8或許能在腸胃道具有抑制發炎的功能。另外在初步添加LZ-8於小鼠腸道表皮細胞株的實驗中，LZ-8有促使它生長的情形，這可能代表LZ-8可以透過調控腸胃道表皮細胞以讓腸胃道維持恆定(homeostasis)。故探討LZ-8腸胃道之中的機制對於治療人類發炎性腸道疾病 (Inflammatory
bowel disease, IBD) 方面或許有開發潛力存在。 | zh_TW |
| dc.description.abstract | LZ-8, a bioactive protein isolated from Ganoderma lucidium, it has been reported that has several immunomodulatory function on immune cells. In our preliminary data showed that orally administering LZ-8 to mice would enhance the increase of CD25+ FOPX3+ regulatory T cell population both in the MLN and spleen. But the mechanism underlying this outcome was remained unknown. In addition, our in vitro data showed that treating LZ-8 to bone marrow-derived regulatory dendritic cells would upregulate the mRNA expression of aldehyde dehydrogenase family 1, subfamily 2 (ALDH1A2), a rate-limiting enzyme that helps dendritic cells synthesis more retinoic acid to exert regulatory function. In the experiment of co-culturing LZ-8-treated regDCs with CD4+ T cells showed higher ratio of FOXP3+ regulatory T cell production. Furthermore, in mice IBD model, LZ-8- fed mice had reduction of criteria for IBD evaluation including weight loss and inflammatory cytokine production. Taken together, these data demonstrated that LZ-8 might activate regulatory dendritic cells residing in intestine (CD103+ DCs), and then promote downstream CD25+ FOXP3+ regulatory T cells development. Furthermore, another source of RA was intestinal epithelial cells (IECs) which express ALDH1A1 and ALDH1A3 to produce RA. In our recent experiment found that adding LZ-8 to mouse IEC cell line, CMT-93, would promote its growth. If LZ-8 could also upregulate the enzymatic activity of ALDH on IECs, it is another good explaination that LZ-8 could attenuate IBD. In conclusion, administration of LZ-8 might mediate the homeostasis in the intestine and have a therapeutic potential to inflammatory disease, such as inflammatory bowel disease. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:25:08Z (GMT). No. of bitstreams: 1 ntu-105-R02449008-1.pdf: 1143387 bytes, checksum: cd01a1583d2d52ceca672a26dda90ec0 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 誌謝 け
中文摘要 げ Abstract こ Abbreviations ご List of figures じ Chapter 1. Introduction 1 1.1 Ling Zhi 8 (LZ-8) 2 1.2 Dendritic Cells 3 1.3 CD103+ Regulatory Dendritic Cells 3 1.4 Regulatory T cells (Tregs) 5 1.5 Inflammatory Bowel Diseases (IBDs) 5 1.6 Intestinal Epithelial Cells (IECs) 6 1.7 Rationale 8 1.8 Specific Aims 9 Chapter 2. Materials and Methods 11 2.1 Mice 12 2.2 Bone marrow-derived DCs culture 12 2.3 Bone marrow-derived reg-DCs culture 12 2.4 Dextran Sulfate Sodium (DSS)-induced Colitis Mice Model 12 2.5 Isolation of intestinal lymphocytes 13 2.6 Isolation of CD11c-positive BMDCs .14 2.7 Isolation of CD4-positive T cells 15 2.8 T cell-DC co-culture 16 2.9 Aldehyde dehydrogenase activity assay 16 2.10 Flow Cytometry 16 2.11 Quantitative real-time PCR 17 2.12 Statistical analysis 18 Chapter 3. Results 19 3.1 LZ-8 affected the aldh1a2 mRNA expression level in BM-derived regulatory DCs. 20 3.2 Effect of LZ-8 on Treg differentiation in co-culture system. 20 3.3 LZ-8 affected the expression of aldehyde dehydrogenase in the small intestine-lamina propria isolated lymphocytes. 20 3.4 Orally administering mice with LZ-8 would ameliroate the DSS-induced colitis symptom by increasing CD4+ CD25+ FOXP3+ Treg population 21 3.5 LZ-8 affected the expression level of RALDH-related genes from total intestinal tissue extraction 21 3.6 Effect of LZ-8 on the mRNA expression of aldh1-3 in CMT-93 22 Chapter 4.Discussion 23 4.1 LZ-8 affected the aldh1a2 mRNA expression level in BM-derived regulatory DCs 24 4.2 Effect of LZ-8 on Treg differentiation in co-culture system 24 4.3 LZ-8 affected the expression of aldehyde dehydrogenase in the small intestine-lamina propria isolated lymphocytes 24 4.4 Orally administering mice with LZ-8 would ameliroate the DSS-induced colitis symptom by increasing CD4+ CD25+ FOXP3+ Treg population 24 4.5 LZ-8 affected the expression level of RALDH-related genes from total intestinal tissue extraction 25 4.6 Effect of LZ-8 on the mRNA expression of aldh1-3 in CMT-93 25 Figures 28 References 41 | |
| dc.language.iso | en | |
| dc.subject | 乙醛脫氫? | zh_TW |
| dc.subject | 蕈菇類免疫調節蛋白 | zh_TW |
| dc.subject | 調節性樹突細胞 | zh_TW |
| dc.subject | 腸道表皮細胞 | zh_TW |
| dc.subject | LZ-8 | en |
| dc.subject | IEC | en |
| dc.subject | regulatory T cell | en |
| dc.subject | regulatory DC | en |
| dc.subject | ALDH | en |
| dc.title | 蕈菇類免疫調節蛋白LZ-8對調節性樹突細胞與腸道表皮細胞的影響 | zh_TW |
| dc.title | The Effect of Fungal Immunomodulatory Protein LZ-8 on Regulatory Dendritic Cells and Intestinal Epithelial Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許秉寧(Ping-Ning Hsu),陳子智(Zih-Jhih Chen) | |
| dc.subject.keyword | 蕈菇類免疫調節蛋白,調節性樹突細胞,腸道表皮細胞,乙醛脫氫?, | zh_TW |
| dc.subject.keyword | LZ-8,regulatory DC,regulatory T cell,IEC,ALDH, | en |
| dc.relation.page | 44 | |
| dc.identifier.doi | 10.6342/NTU201602906 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-18 | |
| 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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