【摘要】： 自身免疫調(diào)節(jié)因子(autoimmune regulator, Aire)是一種轉(zhuǎn)錄調(diào)節(jié)因子,其基因的突變可以導(dǎo)致自身免疫性多腺體綜合征,因此,被認(rèn)為是維持自身免疫耐受的重要分子。Aire在多種淋巴器官中都有表達(dá),尤其在胸腺中表達(dá)較高。胸腺中,Aire主要表達(dá)在胸腺髓質(zhì)上皮細(xì)胞(mTEC)上,其功能是調(diào)節(jié)mTEC外周組織抗原的表達(dá)、清除自身反應(yīng)性T細(xì)胞,在胸腺的陰性選擇、維持中樞自身免疫耐受過程中發(fā)揮重要作用。并且,Aire還可通過促進(jìn)mTEC表達(dá)趨化因子CCL22趨化胸腺細(xì)胞在胸腺中遷移參與陰性選擇。 然而,Aire在外周免疫器官中表達(dá)的生物學(xué)意義還不清楚。我們推測,Aire在外周免疫器官也可能通過調(diào)節(jié)趨化因子的表達(dá),進(jìn)而趨化特定的免疫耐受細(xì)胞群,在維持外周免疫耐受中發(fā)揮作用。 為此,本研究采用Aire轉(zhuǎn)染RAW264.7細(xì)胞的方法,從以下兩個(gè)方面探討了Aire對RAW264.7細(xì)胞中CCL22表達(dá)的影響: 1.首先研究瞬時(shí)轉(zhuǎn)染Aire的RAW264.7細(xì)胞中CCL22表達(dá)變化,研究結(jié)果表明轉(zhuǎn)染Aire后CCL22表達(dá)水平上調(diào)。 2.通過建立穩(wěn)定表達(dá)GFP及GFP-Aire融合蛋白的RAW264.7細(xì)胞系,研究穩(wěn)定表達(dá)Aire的RAW264.7中CCL22表達(dá)變化,結(jié)果顯示該細(xì)胞系中CCL22表達(dá)增加。 本研究通過探討Aire對趨化因子CCL22的影響,為進(jìn)一步研究Aire能否在外周免疫器官通過調(diào)節(jié)趨化因子的表達(dá),進(jìn)而趨化特定的免疫耐受細(xì)胞群,如調(diào)節(jié)性T細(xì)胞(regulatory T cell, Treg),奠定了基礎(chǔ)。為揭示Aire在外周免疫耐受中的作用及其基因突變導(dǎo)致相關(guān)自身免疫病的發(fā)病機(jī)理,開辟了新的思路。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R392

【共引文獻(xiàn)】

相關(guān)博士學(xué)位論文 前2條

1 朱武飛;自身免疫調(diào)節(jié)因子對巨噬細(xì)胞TLRs表達(dá)及其活化類型的影響[D];吉林大學(xué);2011年

2 石亮;自身免疫調(diào)節(jié)因子對大分子自噬及細(xì)胞吞噬功能的影響[D];華中科技大學(xué);2010年

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本文編號(hào)：2480692