The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance

Chuprin Anna; Avin Ayelet; Goldfarb Yael; Herzig Yonatan; Levi Ben; Jacob Adi; Sela Asaf; Katz Shir; Grossman Moran; Guyon Clotilde; Rathaus Moran; Cohen Haim Y.; Sagi Irit; Giraud Matthieu; McBurney Michael W.; Husebye Eystein S.; Abramson Jakub

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The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance

机译：脱乙酰基酶Sirt1是Aire介导的中枢免疫耐受的必需调节剂

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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.

机译：Aire是一种转录调节因子，可在髓样胸腺上皮细胞（mTECs）中诱导成千上万个组织限制性抗原（TRAs）的混杂表达，这是诱导免疫自耐受性的关键步骤。研究提供了有关Aire运作方式的分子见解，但对该过程的更全面的了解仍然难以捉摸。在这里，我们发现成熟的Aire（+）mTECs中蛋白质脱乙酰基酶Sirtuin-1（Sirt1）的大量表达，其中表达Aire依赖的TRA编码基因并随后诱导免疫自耐受性是必需的。我们的研究阐明了Aire介导的转录调控的先前未知的分子机制，并确定了Sirt1在预防器官特异性自身免疫中的独特功能。

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《Nature immunology》 |2015年第7期|共11页
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Chuprin Anna; Avin Ayelet; Goldfarb Yael; Herzig Yonatan; Levi Ben; Jacob Adi; Sela Asaf; Katz Shir; Grossman Moran; Guyon Clotilde; Rathaus Moran; Cohen Haim Y.; Sagi Irit; Giraud Matthieu; McBurney Michael W.; Husebye Eystein S.; Abramson Jakub;
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正文语种 eng
中图分类医学免疫学;
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1. The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance [J] . Chuprin Anna, Avin Ayelet, Goldfarb Yael, Nature immunology . 2015,第7期

机译：脱乙酰基酶Sirt1是Aire介导的中枢免疫耐受的必需调节剂
2. The T cell-specific adapter protein functions as a regulator of peripheral but not central immunological tolerance. [J] . Lapinski PE, MacGregor JN, Marti F, Advances in Experimental Medicine and Biology . 2006,第0期

机译：T细胞特异性衔接蛋白起外周免疫调节剂的作用，但对中枢免疫耐受没有调节作用。
3. Induction of immunologic tolerance to myelin basic protein prevents central nervous system autoimmunity and improves outcome after stroke. [J] . Gee JM, Kalil A, Thullbery M, Stroke: A Journal of Cerebral Circulation . 2008,第5期

机译：诱导对髓鞘碱性蛋白的免疫耐受可预防中枢神经系统自身免疫并改善卒中后的预后。
4. INDUCTION OF ANTIGEN-SPECIFIC IMMUNOLOGICAL TOLERANCE WITH SYNTHETIC NANOPARTICLE VACCINES [C] . Takashi Kei Kishimoto, Petr llyinskii Vaccine technology VI . 2016

机译：合成纳米微粒疫苗对抗原特异性免疫耐受的诱导
5. Acetyltransfer in gene regulation: Structural and biochemical studies of human SIRT1 deacetylase, its FoxO1 substrate, and archaeal PAT acetyltransferase. [D] . Brent, Michael. 2009

机译：基因调控中的乙酰基转移：人SIRT1脱乙酰基酶，其FoxO1底物和古细菌PAT乙酰基转移酶的结构和生化研究。
6. The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice [O] . Jinping Zhang, Sang-Myeong Lee, Stephen Shannon, 2009

机译：III型组蛋白脱乙酰基酶Sirt1对维持小鼠T细胞耐受性至关重要
7. The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice [O] . Zhang, Jinping, Lee, Sang-Myeong, Shannon, Stephen, 2009

机译：III型组蛋白脱乙酰基酶Sirt1对维持小鼠T细胞耐受性至关重要

The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance

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