2014-10-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/643173摘要：半乳醣凝集素-3是半乳醣凝集素蛋白家族的一員，這些蛋白能夠藉著C端的碳水化合物辨認區域與 N-乙醯基乳醣胺結合。半乳醣凝集素-3有非常多樣的功能，包含細胞遷移、附著、細胞凋亡、活化及 吞噬作用等。半乳醣凝集素-3也參與在人類疾病的致病機轉，像是傳染病、自體免疫與發炎相關疾病 和癌症。NKT細胞是先天性免疫的組成之一，根據過去的研究，已知它們在過敏、自體免疫和感染性 疾病中扮演關鍵角色，並調控包括發炎反應在内的各種不同免疫反應。NKT細胞中最主要的一群是非 變異性NKT (iNKT)細胞。非變異性NKT細胞主要藉著它們所分泌的細胞激素來調節各類免疫反應。 當被活化時，iNKT細胞能快速地製造大量的細胞激素，包含丫型干擾素（Th1特有的細胞激素）、介白 質四及介白質十三（Th2特有的細胞激素）和介白質十七（Thl7特有的細胞激素）。過去的研究已知 介白質十七在發炎反應中扮演重要角色。我們先前報導過半乳醣凝集素-3能藉著抑制樹突細胞生成介 白質二十三，以負調控介白質十七的反應。目前為止，科學界對於半乳醣凝集素-3如何調控iNKT細 胞產生細胞激素，和半乳醣凝集素-3在NKT細胞相關疾病的參與角色仍然有許多未知。我們初步的實 驗顯示：半乳醣凝集素-3在iNKT細胞内有高度的表現，並且提示了半乳醣凝集素-3參與在iNKT細 胞内介白質十七的製造過程。在這個計晝，我們將會研究在iNKT細胞中半乳醣凝集素-3本身的調節， 和其調控介白質十七生成的機制。另外，我們將應用實驗老鼠模式，研究在iNKT細胞媒介的呼吸道 及腸胃道發炎反應中，半乳醣凝集素-3的角色與作用機轉。我們預期，從以上研究中所獲得的知識， 將會有助於更深入了解發炎的致病機制，以期發展出新的治療方法。<br> Abstract: Galectin-3 belongs to the galectin family protein which binds N-acetyl-lactosamine through its C-terminal carbohydrate-recognition domains. The functions of galectin-3 are diverse, including cell migration, adhesion, apoptosis, activation and phagocytosis. Galectin-3 is involved in the pathogenesis of human diseases, including infectious, autoimmune and inflammatory diseases and cancer. NKT cell, a component of innate immunity, has been reported to play crucial roles in the pathogenesis of various allergic, autoimmune and infectious diseases and mediate various immune responses including inflammation. The majority of NKT cells are invariant NKT (iNKT) cells. Invariant NKT cells regulate various immune responses largely by the actions of cytokines they secrete. Upon activation, iNKT cells rapidly produce large amounts of cytokines including IFN-y, IL-4 and IL-13, and IL-17 which are Th1-, Th2- and Thl7-specific cytokines, respectively. Importantly, IL-17 has been shown to play an important role in inflammation responses. We have reported that galectin-3 negatively regulates IL-17A responses through inhibition of IL-23/IL-17-axis cytokine production by dendritic cells. Thus far, the regulatory role of galectin-3 in cytokine production by iNKT cells and its relative contribution in NKT cell-mediated diseases are not yet addressed. Our preliminary data show that galectin-3 is highly expressed in iNKT cells and suggest that galectin-3 is involved in IL-17A production by iNKT cells. In this grant proposal, the regulation of galectin-3 in iNKT cells and the mechanism(s) by which galectin-3 regulates IL-17 production in iNKT cells will be investigated. Furthermore, the role of galectin-3 in iNKT cell-mediated airway and gastrointestinal inflammation will be characterized in experimental mouse models. We'll expect the knowledge gained from above studies will bring insights into the pathogenesis of inflammation and allow us develop novel therapeutic treatments.半乳醣凝集素-3iNKT細胞呼吸道發炎腸胃道發炎galectin-3iNKT cellsairway inflammationgastrointestinal inflammation Abstract