Projection of an immunological self shadow within the thymus by the aire protein
Projection of an immunological self shadow within the thymus by the aire protein
复制标题
DOI：
10.1126/science.1075958
复制
发表时间：
2002-11-15
期刊：
影响因子：
56.9
通讯作者：
Mathis, D
中科院分区：
文献类型：
--
作者：
Anderson, MS;Venanzi, ES;Mathis, D
表达有缺陷形式的转录因子AIRE（自身免疫调节因子）的人类发展多器官自身免疫性疾病。我们使用Aire缺陷小鼠来检验这一假设，即该转录因子通过促进外周组织限制性抗原在胸腺髓质上皮细胞中的异位表达来调节自身免疫。这个假设被证明是正确的。突变动物表现出明确的亲。免疫性疾病依赖于胸腺基质细胞中AIRE的缺乏。Aire缺陷的胸腺髓质上皮细胞表现出特异性减少外周抗原编码基因的异位转录。这些发现强调了胸腺施加的“中枢”耐受在控制自身免疫中的重要性。
Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire-deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined pro. le of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.