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  1. NTU Theses and Dissertations Repository
  2. 醫學院
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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80384
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dc.contributor.advisor徐志文(Jr-Wen Shui)
dc.contributor.authorNIEN-SHIN SHIHen
dc.contributor.author施念忻zh_TW
dc.date.accessioned2022-11-24T03:05:33Z-
dc.date.available2021-04-28
dc.date.available2022-11-24T03:05:33Z-
dc.date.copyright2021-04-28
dc.date.issued2021
dc.date.submitted2021-04-22
dc.identifier.citationBishop, J. L., et al. (2014). 'Lyn activity protects mice from DSS colitis and regulates the production of IL-22 from innate lymphoid cells.' Mucosal Immunol 7(2): 405-416. Bohn, E., et al. (1998). 'IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice.' J Immunol 160(1): 299-307. Chassaing, B., et al. (2014). 'Dextran sulfate sodium (DSS)-induced colitis in mice.' Curr Protoc Immunol 104: Unit 15.25. Dudakov, J. A., et al. (2015). 'Interleukin-22: immunobiology and pathology.' Annu Rev Immunol 33: 747-785. Hoytema van Konijnenburg, D. P., et al. (2017). 'Intestinal Epithelial and Intraepithelial T Cell Crosstalk Mediates a Dynamic Response to Infection.' Cell 171(4): 783-794.e713. Huang, L. C. and A. Merchea (2017). 'Dysplasia and Cancer in Inflammatory Bowel Disease.' Surg Clin North Am 97(3): 627-639. Ito, R., et al. (2006). 'Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice.' Clin Exp Immunol 146(2): 330-338. Khor, B., et al. (2011). 'Genetics and pathogenesis of inflammatory bowel disease.' Nature 474(7351): 307-317. Li, L. J., et al. (2014). 'Role of interleukin-22 in inflammatory bowel disease.' World J Gastroenterol 20(48): 18177-18188. Lindemans, C. A., et al. (2015). 'Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration.' Nature 528(7583): 560-564. Munoz, M., et al. (2015). 'Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.' Immunity 42(2): 321-331. Nava, P., et al. (2010). 'Interferon-gamma regulates intestinal epithelial homeostasis through converging beta-catenin signaling pathways.' Immunity 32(3): 392-402. Ng, S. C., et al. (2018). 'Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.' Lancet 390(10114): 2769-2778. Nishida, A., et al. (2012). 'The membrane-bound mucin Muc1 regulates T helper 17-cell responses and colitis in mice.' Gastroenterology 142(4): 865-874.e862. Okamura, H., et al. (1995). 'Cloning of a new cytokine that induces IFN-gamma production by T cells.' Nature 378(6552): 88-91. Ordas, I., et al. (2012). 'Ulcerative colitis.' Lancet 380(9853): 1606-1619. Palmela, C., et al. (2018). 'Adherent-invasive Escherichia coli in inflammatory bowel disease.' Gut 67(3): 574-587. Pan, C. X., et al. (2014). 'Role of interleukin-22 in liver diseases.' Inflamm Res 63(7): 519-525. Pelczar, P., et al. (2016). 'A pathogenic role for T cell-derived IL-22BP in inflammatory bowel disease.' Science 354(6310): 358-362. Pestka, S., et al. (2004). 'Interleukin-10 and related cytokines and receptors.' Annu Rev Immunol 22: 929-979. Pickert, G., et al. (2009). 'STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.' J Exp Med 206(7): 1465-1472. Roussel, P., et al. (2015). 'Investigating the contribution of IL-17A and IL-17F to the host response during Escherichia coli mastitis.' Vet Res 46: 56. Sairenji, T., et al. (2017). 'An Update on Inflammatory Bowel Disease.' Prim Care 44(4): 673-692. Schulz, S. M., et al. (2008). 'Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17.' J Immunol 181(11): 7891-7901. Shtrichman, R. and C. E. Samuel (2001). 'The role of gamma interferon in antimicrobial immunity.' Curr Opin Microbiol 4(3): 251-259. Small, C. L., et al. (2013). 'Persistent infection with Crohn's disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis.' Nat Commun 4: 1957. Sugimoto, K., et al. (2008). 'IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis.' J Clin Invest 118(2): 534-544. Torres, J., et al. (2017). 'Crohn's disease.' Lancet 389(10080): 1741-1755. van de Veerdonk, F. L., et al. (2011). 'Inflammasome activation and IL-1beta and IL-18 processing during infection.' Trends Immunol 32(3): 110-116. Wolk, K., et al. (2004). 'IL-22 increases the innate immunity of tissues.' Immunity 21(2): 241-254. Wonnenberg, B., et al. (2016). 'IL-17A attracts inflammatory cells in murine lung infection with P. aeruginosa.' Innate Immun 22(8): 620-625. Yang, R., et al. (2018). 'IL-12+IL-18 Cosignaling in Human Macrophages and Lung Epithelial Cells Activates Cathelicidin and Autophagy, Inhibiting Intracellular Mycobacterial Growth.' J Immunol 200(7): 2405-2417. Zenewicz, L. A. and R. A. Flavell (2011). 'Recent advances in IL-22 biology.' Int Immunol 23(3): 159-163. Zhang, H. J., et al. (2018). 'IL-17 is a protection effector against the adherent-invasive Escherichia coli in murine colitis.' Mol Immunol 93: 166-172. Zheng, Y., et al. (2008). 'Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens.' Nat Med 14(3): 282-289.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80384-
dc.description.abstract摘要 克隆氏症患者的發炎迴腸黏膜組織中有相當高的機率能夠分離出貼附性侵襲性大腸桿菌(AIEC)。而細菌感染和過度的免疫反應皆為導致發炎性腸道疾病(IBD)的因素,若能釐清與IBD具有高度相關的病原菌感染宿主時會引起的免疫反應能幫助我們更詳細地瞭解IBD的致病過程。一提到協助維持腸道第一道免疫防線的細胞激素就會想到介白素-22(IL-22),表現IL-22受體的腸道上皮細胞在接收到該細胞激素後會促進上皮細胞增生以及誘發抗菌物質的產生。在本篇研究計畫中,我們揭露在飲用DSS水引發腸道發炎的小鼠身上進行AIEC感染時,IL-22會扮演重要的保護角色,B6野生型小鼠感染後可以見到IL-22表現量上升,且IL-22的基因剔除小鼠上會觀察到較高的AIEC含量和較嚴重的腸道發炎情形。然而,透過分析IL-22基因剔除小鼠在DSS-AIEC感染情況下的上皮細胞發現其修復能力較為低落,並伴隨 IL-18、Reg3和CXCL1的表現量下降,且配合我們利用體外organoid培養證實IL-22的刺激能夠促進上皮細胞IL-18、Reg3和CXCL1 mRNA的生成和隱窩毒殺實驗中發現IL-22能夠使抗菌物質從上皮細胞釋放毒殺AIEC來釐清IL-22在DSS-AIEC感染時確切地防禦功能。除此之外,當B6野生型小鼠感染AIEC時除了見到IL-22表現量上升以外上皮細胞IL-18的表現量也會上升,證實IL-22刺激上皮細胞表現IL-18亦為宿主在DSS-AIEC感染防禦的一環,進一步探究其作用機轉和IL-18的防禦功能發現,IL-22作用到腸道上皮細胞後會刺激轉錄因子STAT3的活化使其結合到IL-18 promoter區域促進IL-18基因進行轉錄,而IL-18雖然無法提升抗菌物質mRNA的表現量,但卻能夠促使上皮細胞進行抗菌物質的釋放從上皮細胞釋放殺菌。另外,因著在DSS-AIEC感染的IL-22基因剔除小鼠身上見到固有層淋巴球IFNg和IL-17A的生成降低,我們也透過分別對IFNg和IL-17A的基因剔除小鼠進行相同的感染模型證實,缺乏IFNg或IL-17A的小鼠會有較為嚴重的腸道發炎現象、明顯較高的疾病活動指數和較多的AIEC病原菌的存在,以此說明這兩種細胞激素對於AIEC亦參與在AIEC感染時得宿主防禦。zh_TW
dc.description.provenanceMade available in DSpace on 2022-11-24T03:05:33Z (GMT). No. of bitstreams: 1
U0001-1904202115172600.pdf: 2936202 bytes, checksum: b06d9d3a25dbaaed8ff81315a5eb811b (MD5)
Previous issue date: 2021
en
dc.description.tableofcontents目錄 誌謝.....................................................Ⅰ 中文摘要.................................................Ⅱ 英文摘要.................................................Ⅲ 目錄.....................................................Ⅳ 圖目錄...................................................Ⅴ 緒論......................................................1 研究動機..................................................5 材料與方法................................................6 實驗結果.................................................16 結論.....................................................23 討論.....................................................24 參考文獻.................................................26 圖表.....................................................29 附錄.....................................................47
dc.language.isozh-TW
dc.subject貼附性侵襲性大腸桿菌zh_TW
dc.subject發炎性腸道疾病zh_TW
dc.subjectepithelial protectionen
dc.subjectIL-22en
dc.subjectIL-18en
dc.subjectInflammatory bowel disease(IBD)en
dc.subjectAIECen
dc.title以DSS誘發急性腸炎為模型,探討介白素-22對貼附行性侵襲性大腸桿菌感染之影響zh_TW
dc.titleIL-22 against Crohn’s adherent-invasive Escherichia coli (AIEC) in DSS-induced inflammatory modelen
dc.date.schoolyear109-2
dc.description.degree碩士
dc.contributor.oralexamcommittee李永凌(Hsin-Tsai Liu),張雅貞(Chih-Yang Tseng)
dc.subject.keyword發炎性腸道疾病,貼附性侵襲性大腸桿菌,zh_TW
dc.subject.keywordInflammatory bowel disease(IBD),IL-18,IL-22,AIEC,epithelial protection,en
dc.relation.page50
dc.identifier.doi10.6342/NTU202100840
dc.rights.note同意授權(限校園內公開)
dc.date.accepted2021-04-22
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept微生物學研究所zh_TW
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