2014-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656672摘要：自然殺手 T (NKT) 細胞是一群連結先天性和後天性免疫反應的重要免疫細胞。他們在個體免疫系統中負責對抗自體免疫疾病、感染疾病和癌症的發展。c-Maf屬於 bZip 轉錄因子中Maf家族蛋白的一員。c-Maf起初被證實會專一性地表現在輔助T第二型 (Th2) 細胞中，負責誘導介白素四 (IL-4) 基因的表現並且對於輔助 T第二型細胞的分化走向是重要的。最近研究指出 c-Maf也會表現在輔助 T第十七型 (Th17) 細胞和濾泡輔助型 T (Tfh) 細胞中，其會正向調控介白素二十一 (IL-21) 基因表現但是卻負向調控介白素二十二 (IL-22) 的分泌。此外 c-Maf也會調節經由脂多醣(LPS) 活化的巨噬細胞中介白素十 (IL-10) 的產生。我們先前的研究證實 c-Maf會經過 SUMOylation 蛋白質轉譯後修飾降低其對介白素四基因的轉錄能力。自然殺手 T細胞經由-galactosylceramide (-GalCer) 刺激後會快速產生干擾素(IFN-) 和介白素四。最近許多研究也證實在某些生理環境下，自然殺手 T細胞會產生輔助 T 第十七型細胞相關的細胞激素，像是介白素十七、二十一及二十二。雖然 c-Maf在輔助 T第二型、輔助 T第十七型、濾泡輔助型 T細胞和巨噬細胞中調控許多細胞激素的分泌，其在自然殺手 T細胞的細胞激素基因表現以及在自然殺手 T細胞調節的疾病中扮演的角色仍不清楚。在本計畫中，我們將完成下列實驗目標：(一)釐清 c-Maf在自然殺手 T細胞內的表現，(二)研究 c-Maf在自然殺手 T細胞中如何調控細胞激素的表現，(三)研究 c-Maf在自然殺手 T細胞調節的小鼠疾病模式中扮演的角色。由本計畫所得到的實驗結果將可進一步了解自然殺手 T細胞如何透過抗原-c-Maf-介白素十七或介白素四訊息傳遞路徑去調控個體的先天性免疫及黏膜性免疫。<br> Abstract: NKT cells are a subset of lymphocytes that bridge the innate and adaptive immunity. They are important immune cells that contribute to the defense against autoimmunity and cancer development. c-Maf is belong to Maf family protein which is a subgroup of the basic leucine zipper (bZip) transcription factors. It was first known that c-Maf is exclusively expressed in Th2 cells, but not Th1 cells, to induce IL-4 expression and is critical to Th2 commitment. Recent studies indicated that c-Maf is also expressed in Th17 and Tfh cells and it positively regulates IL-21 gene expression whereas it negatively mediates IL-22 production. Furthermore, c-Maf regulates the IL-10 production in LPS-activated macrophages. Our previous studies further demonstrated that SUMOylation, a post-translational modification, of c-Maf, attenuates its transactivity on IL-4 gene expression. It is well known that NKT cells can produce IFN- and IL-4 upon -galactosylceramide (-GalCer) stimulation. Recent studies had shown that NKT cells also produce Th17-related cytokines such as IL-17A, IL-17F, IL-21 and IL-22 in certain physiological conditions. Although c-Maf plays an important role in regulation of cytokine production in Th2, Th17, Tfh cells and macrophage, its role in cytokine gene expression by NKT cells and the relative contribution of c-Maf in NKT-mediated diseases are not yet addressed. In this study, we have the following specific aims: (1) characterizing the expression of c-Maf in NKT cells, (2) studying the functional role of c-Maf on cytokine production in NKT cells, and (3) investigating the role of c-Maf in NKT cells-mediated disease mouse models. The knowledge thus gained from the proposed studies will bring important insights into the role of antigen-c-Maf-IL-17 or IL-4 axis in NKT cells in the regulation of innate and mucosal immunity.Water Supply SystemPerformance Evaluation IndicatorsSource WaterWater Treatment PlantWater Distribution System