The cellular mechanism of Aire control of T cell tolerance
The cellular mechanism of Aire control of T cell tolerance
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DOI：
10.1016/j.immuni.2005.07.005
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发表时间：
2005-08-01
期刊：
影响因子：
32.4
通讯作者：
Mathis, D
中科院分区：
文献类型：
--
作者：
Anderson, MS;Venanzi, ES;Mathis, D
Aire 通过诱导胸腺髓质上皮细胞中一系列外周组织抗原的表达来促进胸腺细胞的耐受性。我们证明，Aire 发挥其耐受促进功能的细胞机制主要不是调节性 T 细胞的正选择，而是效应 T 细胞的负选择。令人惊讶的是，Aire 补充了其对编码外周组织抗原的基因转录的影响，以某种方式增强了髓质上皮细胞的抗原呈递能力。因此，这种转录控制元件通过为特定的胸腺基质细胞类型提供自身抗原库以及通过更好地武装此类细胞以将这些抗原呈递给分化的胸腺细胞来促进中枢耐受。在艾尔缺席的情况下，就会出现自身免疫性疾病，并最终出现明显的自身免疫性疾病。
Aire promotes the tolerization of thymocytes by inducing the expression of a battery of peripheral-tissue antigens in thymic medullary epithelial cells. We demonstrate that the cellular mechanism by which Aire exerts its tolerance-promoting function is not primarily positive selection of regulatory T cells, but rather negative selection of T effector cells. Surprisingly, supplementing its influence on the transcription of genes encoding peripheral-tissue antigens, Aire somehow enhances the antigen-presentation capability of medullary epithelial cells. Thus, this transcriptional control element promotes central tolerance both by furnishing a specific thymic stromal cell type with a repertoire of self antigens and by better arming such cells to present these antigens to differentiating thymocytes. In Aire's absence, autoimmunity and ultimately overt autoimmune disease develops.