The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance
The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance
复制标题
DOI：
10.1038/ni.3194
复制
发表时间：
2015-07-01
影响因子：
30.5
通讯作者：
Abramson, Jakub
中科院分区：
文献类型：
--
作者：
Chuprin, Anna;Avin, Ayelet;Abramson, Jakub
Aire是一种转录调节因子，可诱导胸腺髓质上皮细胞（mTECs）中数千种组织限制性抗原（TRAs）的混杂表达，这是诱导免疫自身耐受的关键步骤。研究已经提供了关于Aire如何运作的分子见解，但对这一过程的更全面理解仍然难以捉摸。在此，我们发现在成熟的Aire（+）mTEC中大量表达蛋白质脱乙酰酶Sirtuin-1（Sirt 1），其中它是Aire依赖性TRA编码基因表达和随后诱导免疫自身耐受所必需的。我们的研究阐明了一个以前未知的分子机制Aire介导的转录调控，并确定了一个独特的功能Sirt 1在防止器官特异性自身免疫。
Aire is a transcriptional regulator that induces the promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for the induction of immunological self-tolerance. Studies have offered molecular insights into how Aire operates, but more comprehensive understanding of this process still remains elusive. Here we found abundant expression of the protein deacetylase Sirtuin-1 (Sirt1) in mature Aire(+) mTECs, wherein it was required for the expression of Aire-dependent TRA-encoding genes and the subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and identifies a unique function for Sirt1 in preventing organ-specific autoimmunity.