Chan Alice Y, Anderson Mark S
Diabetes Center.
Department of Pediatrics, University of California, San Francisco, San Francisco, California.
Ann N Y Acad Sci. 2015 Nov;1356(1):80-9. doi: 10.1111/nyas.12960.
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 has 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.
自身免疫调节因子（Aire）最初被鉴定为导致人类多器官系统自身免疫的基因，在小鼠中删除该基因也会导致器官特异性自身免疫。Aire调节胸腺髓质上皮细胞（mTECs）中组织特异性抗原（TSAs）的表达，这在自身反应性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发育中的作用有助于阐明其呈现预防自身免疫所需的TSAs谱的能力。Aire功能域的分子特征揭示了多个结合伙伴，它们协助Aire在改变基因转录和染色质重塑方面的功能。这些最新进展进一步凸显了Aire在中枢耐受中的重要性。
