Aire-mediated mechanism of tolerance against Dsg3, the autoantigen in pemphigus vulgaris

艾尔介导的针对寻常型天疱疮自身抗原 Dsg3 的耐受机制

• 批准号: 21791093
• 负责人: WADA Naoko
• 金额: $ 2.75万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791093/
• 关键词: Aire; 天疱瘡; 免疫寛容; 胸腺

The transcription factor Aire promotes the expression of a wide range of peripheral organ-specific antigens in the thymus, which will serve as self-antigens in negative selection. We demonstrated desmoglein 3 (Dsg3), the autoantigen in pemphigus vulgaris, expressed in mouse thymus dependent on Aire. Aire^<-/-> T cells, but not Aire^<+/+> T cells, induced low levels of anti-Dsg3 IgG production when transferred with Dsg3^<-/-> B cells in Rag2^<-/-> recipient mice. These findings suggest that Aire plays a role in tolerance against Dsg3 through the selection of T cells in thymus.

转录因子Aire促进胸腺中广泛的外周器官特异性抗原的表达，这些抗原将在负选择中作为自身抗原。我们发现寻常型天疱疮自身抗原桥粒芯糖蛋白3(Dsg3)依赖于Aire在小鼠胸腺中表达。Aire^&lt；-/-&gt；T细胞，而不是Aire^&lt；+/+&gt；T细胞，当与Dsg3^&lt；-/-&gt；B细胞一起转移时，在Rag2^&lt；-/-&gt；小鼠体内诱导低水平的抗Dsg3抗体产生。这些发现表明，Aire通过选择胸腺中的T细胞在对Dsg3的耐受中发挥作用。

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Aire-Dependent Thymic Expression of Desmoglein 3, the Autoantigen in Pemphigus Vulgaris, and Its Role in T-Cell Tolerance

• DOI: 10.1038/jid.2010.330
• 发表时间: 2011-02-01
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Wada, Naoko;Nishifuji, Koji;Amagai, Masayuki
• 通讯作者: Amagai, Masayuki