Central tolerance to self revealed by the autoimmune regulator
Central tolerance to self revealed by the autoimmune regulator
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DOI：
10.1111/nyas.12960
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Anderson, Mark S.
中科院分区：
文献类型：
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作者：
Chan, Alice Y.;Anderson, Mark S.
自身免疫调节基因(Aire)最初被认为是导致人类多器官系统自身免疫的基因，而在小鼠中该基因的缺失也导致了器官特异性自身免疫。AIRE调节髓质胸腺上皮细胞(MTECs)组织特异性抗原(TSAs)的表达，在自身反应性T细胞的阴性选择和调节性T细胞的产生中起关键作用。最近，Aire在mTECs发展中的作用有助于阐明其呈现预防自身免疫所需的TSA谱的能力。对Aire功能区的分子表征揭示了Aire的多个结合伙伴，它们帮助Aire改变基因转录和染色质重塑。最近的这些进展进一步强调了Aire在中枢耐受中的重要性。
The autoimmune regulator (Aire) was initially identified as the gene causing multiorgan system autoimmunity in humans, and deletion of this gene in mice also resulted in organ-specific autoimmunity. Aire regulates the expression of tissue-specific antigens (TSAs) in medullary thymic epithelial cells (mTECs), which play a critical role in the negative selection of autoreactive T cells and the generation of regulatory T cells. More recently, the role of Aire in the development of mTECs have helped elucidate its ability to present the spectrum of TSAs needed to prevent autoimmunity. Molecular characterization of the functional domains of Aire has revealed multiple binding partners that assist Aire's function in altering gene transcription and chromatin remodeling. These recent advances have further highlighted the importance of Aire in central tolerance.