权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Roles of the Autoimmune Regulator (AIRE) Gene in Immune Response

自身免疫调节基因 (AIRE) 在免疫反应中的作用

基本信息

批准号：
11694314
负责人：
SHIMIZU Nobuyoshi
金额：
$ 8.19万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11694314/
关键词：
APECED APS-1 AIRE Autoimmune disease Thymus Antigen presenting cells CBP Dendritic cells SV40T抗原トランスジェニックマウス免疫応答 RelB 転写調節因子

项目摘要

1. AIRE gene expression: We have investigated the expression of the AIRE gene by mRNA in situ hybridization and immunohistochemistry in various human tissues. We showed that AIRE is expressed in distinct cells in thymus medulla, and also in rare cells in lymph node paracortex and medulla, and in spleen and fetal liver. By RT-PCR AIRE mRNA was detected not only in thymus, lymph node, spleen and testis but also in most human and mouse tissues analyzed. We also found that the AIRE gene is restrictively expressed in the peripheral monocyte/dendritic cell lineage.2. Structure and function of AIRE protein: We showed that AIRE fused to a heterologous DNA binding domain activates transcription from a reporter promoter. We also showed that AIRE forms homodimers through the HSR domain and interacts with common transcriptional co-activator CREB-binding protein (CBP) in vitro and in yeast nuclei through the CH1 and CH3 conserved domains of CBP.3. AIRE gene mutations in APECED patients: We have identified four novel AIRE gene mutations in two Japanese families with APECED.4. Establishment of AIRE-expressing cell line: To establish permanent lines of "AIRE-expressing cells", we produced a transgenic mouse expressing SV40 T-antigens driven by mouse AIRE gene promoter. We isolated cells from thymus of the transgenic mouse and maintained them in culture from which we established immortalized cells. These immortalized AIRE cells are extremely useful in studies on the molecular aspects of AIRE gene functions.

1. AIRE基因表达：我们已经研究了AIRE基因的mRNA原位杂交和免疫组织化学在各种人体组织中的表达。我们发现AIRE在胸腺髓质的不同细胞中表达，也在淋巴结副皮质和髓质的稀有细胞中表达，以及在脾和胎肝中表达。RT-PCR检测到AIRE mRNA不仅在胸腺、淋巴结、脾脏和睾丸中，而且在所分析的大多数人和小鼠组织中也有表达。我们还发现AIRE基因在外周血单核细胞/树突状细胞系中限制性表达. AIRE蛋白的结构和功能：我们发现，AIRE融合到异源DNA结合结构域激活从报告基因启动子的转录。我们还发现AIRE通过HSR结构域形成同源二聚体，并通过CBP的CH 1和CH 3保守结构域在体外和酵母细胞核中与共同的转录共激活因子CREB结合蛋白（CBP）相互作用。APECED患者的AIRE基因突变：我们在两个日本APECED家族中发现了四种新的AIRE基因突变。AIRE表达细胞系的建立：为了建立“AIRE表达细胞”的永久系，我们产生了由小鼠AIRE基因启动子驱动的表达SV 40 T抗原的转基因小鼠。我们从转基因小鼠的胸腺中分离细胞，并将其保持在培养物中，从该培养物中我们建立了永生化细胞。这些永生化AIRE细胞在AIRE基因功能的分子方面的研究中是非常有用的。