自身免疫调节因子对RAW264.7细胞中CCL22表达影响的研究
发布时间：2019-05-19 11:29
【摘要】： 自身免疫调节因子(autoimmune regulator, Aire)是一种转录调节因子,其基因的突变可以导致自身免疫性多腺体综合征,因此,被认为是维持自身免疫耐受的重要分子。Aire在多种淋巴器官中都有表达,尤其在胸腺中表达较高。胸腺中,Aire主要表达在胸腺髓质上皮细胞(mTEC)上,其功能是调节mTEC外周组织抗原的表达、清除自身反应性T细胞,在胸腺的阴性选择、维持中枢自身免疫耐受过程中发挥重要作用。并且,Aire还可通过促进mTEC表达趋化因子CCL22趋化胸腺细胞在胸腺中迁移参与阴性选择。 然而,Aire在外周免疫器官中表达的生物学意义还不清楚。我们推测,Aire在外周免疫器官也可能通过调节趋化因子的表达,进而趋化特定的免疫耐受细胞群,在维持外周免疫耐受中发挥作用。 为此,本研究采用Aire转染RAW264.7细胞的方法,从以下两个方面探讨了Aire对RAW264.7细胞中CCL22表达的影响: 1.首先研究瞬时转染Aire的RAW264.7细胞中CCL22表达变化,研究结果表明转染Aire后CCL22表达水平上调。 2.通过建立稳定表达GFP及GFP-Aire融合蛋白的RAW264.7细胞系,研究稳定表达Aire的RAW264.7中CCL22表达变化,结果显示该细胞系中CCL22表达增加。 本研究通过探讨Aire对趋化因子CCL22的影响,为进一步研究Aire能否在外周免疫器官通过调节趋化因子的表达,进而趋化特定的免疫耐受细胞群,如调节性T细胞(regulatory T cell, Treg),奠定了基础。为揭示Aire在外周免疫耐受中的作用及其基因突变导致相关自身免疫病的发病机理,开辟了新的思路。
[Abstract]:Autoimmune regulatory factor (autoimmune regulator, Aire) is a transcriptional regulator whose gene mutation can lead to autoimmune polygland syndrome. Therefore, Aire is considered to be an important molecule to maintain autoimmune tolerance. Aire is expressed in a variety of lymphoid organs, especially in the thymic gland. In the thymic gland, Aire is mainly expressed on the thymic medulla epithelial cell (mTEC). Its function is to regulate the expression of mTEC peripheral tissue antigen, clear the autoreactive T cells, and negative selection in the thymic gland. It plays an important role in maintaining central autoimmune tolerance. In addition, Aire can also participate in negative selection by promoting the migration of chemokine CCL22 chemotactic thymocytes in the thymic gland by promoting the expression of mTEC. However, the biological significance of Aire expression in peripheral immune organs is not clear. We speculate that Aire may also play a role in maintaining peripheral immune tolerance by regulating the expression of chemokines and chemotactic specific groups of immune tolerant cells. In this study, the effect of Aire on the expression of CCL22 in RAW264.7 cells was investigated from the following two aspects: 1. Firstly, the expression of CCL22 in RAW264.7 cells transfected with Aire was studied. The results showed that the expression level of CCL22 was up-regulated after Aire transfer. 2. Through the establishment of RAW264.7 cell line stably expressing GFP and GFP-Aire fusion protein, the expression of CCL22 in RAW264.7 stably expressing Aire was studied. The results showed that the expression of CCL22 in the cell line was increased. In this study, the effect of Aire on chemokine CCL22 was studied in order to further study whether Aire can chemotactic specific immune tolerant cell groups, such as regulatory T cell (regulatory T cell, Treg), by regulating the expression of chemokines in peripheral immune organs. The foundation was laid. In order to reveal the role of Aire in peripheral immune tolerance and the pathogenesis of autoimmune diseases caused by gene mutation, a new idea was opened up.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R392
本文编号：2480692
[Abstract]:Autoimmune regulatory factor (autoimmune regulator, Aire) is a transcriptional regulator whose gene mutation can lead to autoimmune polygland syndrome. Therefore, Aire is considered to be an important molecule to maintain autoimmune tolerance. Aire is expressed in a variety of lymphoid organs, especially in the thymic gland. In the thymic gland, Aire is mainly expressed on the thymic medulla epithelial cell (mTEC). Its function is to regulate the expression of mTEC peripheral tissue antigen, clear the autoreactive T cells, and negative selection in the thymic gland. It plays an important role in maintaining central autoimmune tolerance. In addition, Aire can also participate in negative selection by promoting the migration of chemokine CCL22 chemotactic thymocytes in the thymic gland by promoting the expression of mTEC. However, the biological significance of Aire expression in peripheral immune organs is not clear. We speculate that Aire may also play a role in maintaining peripheral immune tolerance by regulating the expression of chemokines and chemotactic specific groups of immune tolerant cells. In this study, the effect of Aire on the expression of CCL22 in RAW264.7 cells was investigated from the following two aspects: 1. Firstly, the expression of CCL22 in RAW264.7 cells transfected with Aire was studied. The results showed that the expression level of CCL22 was up-regulated after Aire transfer. 2. Through the establishment of RAW264.7 cell line stably expressing GFP and GFP-Aire fusion protein, the expression of CCL22 in RAW264.7 stably expressing Aire was studied. The results showed that the expression of CCL22 in the cell line was increased. In this study, the effect of Aire on chemokine CCL22 was studied in order to further study whether Aire can chemotactic specific immune tolerant cell groups, such as regulatory T cell (regulatory T cell, Treg), by regulating the expression of chemokines in peripheral immune organs. The foundation was laid. In order to reveal the role of Aire in peripheral immune tolerance and the pathogenesis of autoimmune diseases caused by gene mutation, a new idea was opened up.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R392
【共引文献】
相关博士学位论文 前2条
1 朱武飞;自身免疫调节因子对巨噬细胞TLRs表达及其活化类型的影响[D];吉林大学;2011年
2 石亮;自身免疫调节因子对大分子自噬及细胞吞噬功能的影响[D];华中科技大学;2010年
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