Which model better fits the role of aire in the establishment of self-tolerance: the transcription model or the maturation model?
Which model better fits the role of aire in the establishment of self-tolerance: the transcription model or the maturation model?
复制标题
哪个模型更适合 aire 在自我耐受建立中的作用：转录模型还是成熟模型？
DOI：
10.3389/fimmu.2013.00210
复制
发表时间：
2013
影响因子：
7.3
通讯作者：
Mouri Y
中科院分区：
文献类型：
--
作者：
Matsumoto M;Nishikawa Y;Nishijima H;Morimoto J;Matsumoto M;Mouri Y
Aire依赖的转录控制许多组织限制性自身抗原（TRA）基因在胸腺髓质上皮细胞（髓质胸腺上皮细胞，mTECs）的发现提出了一个有趣的问题，如何单一的Aire基因可以影响如此大量的TRA基因在mTECs的转录。从机械论的观点来看，有两种可能的模型来解释Aire在这一行动中的作用。在第一个模型中，TRAs被认为是Aire转录活性的直接靶基因。在这种情况下，细胞内缺乏Aire蛋白将导致TRA基因表达缺陷，而mTEC的成熟程序原则上不受影响。第二个模型假设Aire对于mTEC的成熟程序是必要的。在这种情况下，我们假设mTEC隔室在没有Aire的情况下不会正常成熟。如果TRA基因表达特性的获得取决于mTEC的成熟状态，则Aire缺陷型mTEC中这种Aire依赖性成熟程序的缺陷也可导致TRA基因表达受损。在这篇简短的综述中，我们将集中在这两个对比模型中的作用，Aire在控制表达的TRAs内mTECs。
The discovery of Aire-dependent transcriptional control of many tissue-restricted self-antigen (TRA) genes in thymic epithelial cells in the medulla (medullary thymic epithelial cells, mTECs) has raised the intriguing question of how the single Aire gene can influence the transcription of such a large number of TRA genes within mTECs. From a mechanistic viewpoint, there are two possible models to explain the function of Aire in this action. In the first model, TRAs are considered to be the direct target genes of Aire’s transcriptional activity. In this scenario, the lack of Aire protein within cells would result in the defective TRA gene expression, while the maturation program of mTECs would be unaffected in principle. The second model hypothesizes that Aire is necessary for the maturation program of mTECs. In this case, we assume that the mTEC compartment does not mature normally in the absence of Aire. If acquisition of the properties of TRA gene expression depends on the maturation status of mTECs, a defect of such an Aire-dependent maturation program in Aire-deficient mTECs can also result in impaired TRA gene expression. In this brief review, we will focus on these two contrasting models for the roles of Aire in controlling the expression of TRAs within mTECs.