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標題: | Syk於腸道表皮細胞介白素-22訊息傳遞及維持腸道表皮完整性中扮演之角色 The role of Syk in intestinal epithelial IL-22 signaling pathway and in the gut integrity maintenance |
作者: | Mu-Yun Lin 林牧昀 |
指導教授: | 朱清良 |
關鍵字: | 脾酪胺酸激?,腸道表皮細胞,腸炎,介白素-22,抗微生物?,黏膜蛋白, spleen tyrosine kinase (Syk),intestinal epithelial cell,inflammatory bowel disease (IBD),Interleukin 22 (IL-22),antimicrobial peptide (AMP),mucin, |
出版年 : | 2016 |
學位: | 碩士 |
摘要: | 脾酪氨酸激酶(spleen tyrosine kinase, Syk)在免疫細胞裡的表現及功能在過去被廣泛研究,並發現它能參與許多免疫反應及細胞活化等的訊息傳遞。報導指出Syk 也存在於其他多種細胞內,但在腸道表皮細胞(intestinal epithelial cells)功能卻仍不清楚。腸道表皮細胞作為腸內菌及腸道免疫系統的屏障,對於腸道生理系統穩定的維持具有重要的作用,若功能缺失可能造成發炎性腸道疾病(inflammatory bowel disease, IBD)。為了研究Syk 在腸道表皮細胞的功能,我們生產出專一在腸道表皮細胞中缺乏Syk 的小鼠Sykflox/flox x Vil-cre,Syk△IEC),然後發現在葡聚醣硫酸鈉(dextran sulfate sodium, DSS)引發腸炎的實驗模式中,此Syk 缺失的小鼠發炎情形會較野生型(WT)嚴重。接著我們想看Syk 的缺失是否會造成腸道表皮細胞容易進行細胞凋亡(apoptosis),進一步導致更嚴重的腸炎。另外,我們想研究Syk 究竟參與哪一條訊息傳遞路徑,影響腸表皮細胞的功能。文獻指出介白素-22 (Interleukin-22, IL-22)可促進腸道細胞產生抗微生物肽(antimicrobial peptide, AMP)及黏膜蛋白(mucin),減緩腸道發炎的情形;且報導指出IL-22 能藉由活化STAT3 及其他激酶,以調控細胞功能。此篇研究中,我們發現Syk 可能藉由參與IL-22-STAT3 的訊息傳遞,促進腸道表皮細胞產生抗微生物肽及黏膜蛋白,以維持腸道系統的恆定。 Spleen tyrosine kinase (Syk) is widely implicated in several immune responses and cell activation in various hematopoietic cells. While being detected in other tissues, the role and function of Syk in intestinal epithelial cells are still elusive. Intestinal epithelium functions as an essential barrier for maintenance of mucosal homeostasis, and its dysregulation causes the development of IBD. To study the function of Syk in intestinal epithelium, we generate mice with Syk-deficient intestinal epithelial cells (vil-cre x sykflox/flox, Syk△IEC), and then we demonstrate that the transgenic mice are more sensitive to DSS-induced colitis. Next, we examine whether Syk-deficiency contributes to the increased apoptosis of intestinal epithelial cells and thus to the exaggeration of experimental colitis. Moreover, we would like to investigate which signaling pathway Syk may be involved in and hence affect the function of intestinal epithelial cells. The interleukin 22 (IL-22) is known for ameliorating colitis through enhancing the production of intestinal antimicrobial peptides (AMPs) and mucin. The cytokine acts on its target cell via activating STAT3 and several other kinases. Here we found that Syk may play a positive role in IL-22-STAT3 pathway and also in the mucin and AMP production by intestinal epithelial cells. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49352 |
DOI: | 10.6342/NTU201602751 |
全文授權: | 有償授權 |
顯示於系所單位: | 免疫學研究所 |
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