自身免疫调节因子（autoimmune regulator，AIRE）具有调控胸腺内组织限制性抗原（tissue restricted antigens，TRAs）表达，诱导免疫耐受的功能。因此，本课题设想将AIRE转导至骨髓DCs细胞中，模拟其在胸腺中的作用，探索合理、有效诱导自身免疫耐受的方式。 研究内容包括:1.采用基因转导技术将AIRE转导至DCs，体内外观察AIRE对DCs细胞TRAs表达调控的影响；2.利用AIRE转导的骨髓DCs细胞移植，观察对受者NOD鼠糖尿病发生的影响，评估AIRE通过调控TRAs表达诱导免疫耐受的效果；3.通过体外和体内两方面分析AIRE调控TRAs对自身反应性T细胞清除和Treg细胞产生的影响，探究AIRE通过调控TRAs诱导免疫耐受的机制。 人工诱导免疫耐受方式的建立对防治自身免疫病、移植排斥反应、过敏反应等具有重要的生物学意义和临床应用价值。

Autoimmune regualtor (AIRE) participates in immune tolerance by regulating the expressions of tissue restricted antigens (TRAs) in thymus. Therefore, we suppose that if the immune tolerance could be induced by exploring the resonable, effective approach that AIRE is transduced into bone marrow dendritic cells (DCs) and plays its function as thymus. The study include:1. The effects of AIRE on the expressions of TRAs will be observed in vivo and in vitro by tansducing AIRE into DCs with gene transduction technique.2. The establishment of the immune tolerance induced through regulating TRAs by AIRE will be evaluated by occurrence of diabetes in recipient NOD mice that are transplanted by AIRE transduced bone marrow DCs.3. The mechanisms of AIRE in inducing immune tolerance by regulating TRAs will be explored by analyzing the deletion of autoreactive T cells and generation of Treg. To establish artifical approach of immune tolerance has important biological significance and clinical application value for prevention and treatment of autoimmune disease, transplantation rejection, allergic reation and so on.