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Title: | 探討c-Maf在不變自然殺手T細胞之細胞激素基因表現中所扮演的角色 The Role of c-Maf in Cytokine Gene Expression in Invariant Natural Killer T Cells |
Authors: | Jhang-Sian Yu 游彰憲 |
Advisor: | 繆希椿(Shi-Chuen Miaw) |
Keyword: | 不變自然殺手T細胞,c-Maf,介白素-17,細胞激素調控,呼吸道嗜中性球增多, invariant natural killer T cells,c-Maf,IL-17,cytokine regulation,airway neutrophilia, |
Publication Year : | 2018 |
Degree: | 博士 |
Abstract: | c-Maf屬於large Maf家族轉錄因子的一員,其對於第二型、第十七型、濾泡型輔助T細胞以及第一型調節性T細胞之細胞激素產生與分化過程的調節扮演重要的角色。不變自然殺手T細胞在接受其專一性醣脂質抗原-galactosylceramide (-GalCer) 的刺激後能快速地產生輔助型T細胞相關之細胞激素,例如:干擾素-、介白素-4及介白素-17。然而c-Maf在不變自然殺手T細胞及其所調節的疾病中所扮演的角色仍然是未知的。在本研究中,我們證實不變自然殺手T細胞在經由-GalCer刺激後會表現c-Maf轉錄本及蛋白。利用c-Maf缺失之胎鼠肝細胞重建小鼠進一步證明c-Maf缺失之不變自然殺手T細胞,相較於野生型不變自然殺手T細胞,在接收-GalCer刺激後會產生較少量的介白素-17A。雖然c-Maf基因缺失不會影響不變自然殺手T細胞的發育過程與活化狀態,但c-Maf對於不變自然殺手T細胞受到微環境中的介白素-6、介白素-1以及轉化生長因子- 誘導成第十七型不變自然殺手T細胞的過程以及RORt的最佳表現量是不可缺的。因此,c-Maf缺失之第十七型不變自然殺手T細胞失去其吸引嗜中性球遷移到肺臟的能力。總結來說,c-Maf在第十七型不變自然殺手T細胞中對於介白素-17A及RORt的表現扮演了正向調節的角色。對於由第十七型不變自然殺手T細胞所調節的發炎疾病,提供了一個具有潛力的治療目標。 c-Maf belongs to the large Maf family of transcription factors and plays a key role in the regulation of cytokine production and differentiation of TH2, TH17, TFH and Tr1 cells. Invariant natural killer T (iNKT) cells can rapidly produce large quantity of TH-related cytokines such as IFN-, IL-4 and IL-17A upon stimulation by glycolipid antigens, such as -galactosylceramide (-GalCer). However, the role of c-Maf in iNKT cells and iNKT cells-mediated diseases remains poorly understood. In this study, we demonstrate that -GalCer-stimulated iNKT cells express c-Maf transcript and protein. By using c-Maf-deficient fetal liver cell-reconstituted mice, we further show that c-Maf-deficient iNKT cells produce less IL-17A than their wild-type (WT) counterparts after -GalCer stimulation. While c-Maf deficiency does not affect the development and activation of iNKT cells, c-Maf is essential for the induction of IL-17-producing iNKT (iNKT17) cells by IL-6, TGF- and IL-1, and the optimal expression of RORt. Therefore, c-Maf-deficient iNKT17 cells lose the ability to recruit neutrophils into the lungs. Taken together, c-Maf is a positive regulator for the expression of IL-17A and RORt in iNKT17 cells. It is a potential therapeutic target in iNKT17 cell-mediated inflammatory disease. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70143 |
DOI: | 10.6342/NTU201800236 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 免疫學研究所 |
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ntu-107-1.pdf Restricted Access | 9.86 MB | Adobe PDF |
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