Deacetylase inhibitor trichostatin A down-regulates Foxp3 expression and reduces CD4+CD25+ regulatory T cells
Deacetylase inhibitor trichostatin A down-regulates Foxp3 expression and reduces CD4+CD25+ regulatory T cells
复制标题
脱乙酰酶抑制剂曲古抑菌素 A 下调 Foxp3 表达并减少 CD4 CD25 调节性 T 细胞。
DOI：
10.1016/j.bbrc.2010.08.090
复制
发表时间：
2010-09-24
影响因子：
3.1
通讯作者：
Sun, Jian
中科院分区：
文献类型：
--
作者：
Liu, Zhijian;Zhang, Chenquan;Sun, Jian
叉头转录因子Foxp 3对CD 4（+）CD 25（+）调节性T（Treg）细胞的发育和功能至关重要，所述调节性T（Treg）细胞起维持免疫耐受和预防自身免疫的作用。赖氨酸乙酰化由赖氨酸乙酰转移酶和赖氨酸脱乙酰化酶调节，在基因转录和蛋白质功能中起重要作用。据报道，赖氨酸脱乙酰酶抑制剂甲氨蝶呤（TSA）在体内上调Foxp 3表达并增加CD 4（+）CD 25（+）Treg细胞的产生。相反，我们发现TSA在体外显著降低Foxp 3 mRNA和蛋白水平。此外，TSA增强了Foxp 3启动子的活性，但增加了Foxp 3 mRNA的衰减。此外，TSA的施用显著损害了C57 BL/6 J小鼠中Foxp 3的表达并减少了CD 4（+）CD 25（+）Foxp 3（+）Treg细胞的数量。因此，我们的结果表明，TSA通过体外诱导mRNA降解来降低Foxp 3的表达。我们的结果与之前的报告不一致，这些报告已进行了讨论（C）2010 Elsevier Inc保留所有权利
The forkhead transcription factor Foxp3 is essential for the development and function of CD4(+)CD25(+) regulatory T (Treg) cells, which act to maintain immune tolerance and prevent autoimmunity Lysine acetylation that is regulated by lysine acetyltransferases and lysine deacetylases plays an important role in gene transcription and protein function. Lysine deacetylase inhibitor trichostatin A (TSA) is reported to up-regulate Foxp3 expression and increase the generation of CD4(+)CD25(+) Treg cells in vivo In contrast, we found that TSA dramatically reduced the levels of Foxp3 mRNA and protein in vitro. Moreover, TSA enhanced the activity of the Foxp3 promoter but increased the decay of Foxp3 mRNA. Furthermore, administration of TSA significantly impaired the expression of Foxp3 and reduced the number of CD4(+)CD25(+)Foxp3(+) Treg cells in C57BL/6J mice Thus, our results show that TSA reduces the expression of Foxp3 through induction of mRNA degradation in vitro Accordingly, TSA decreases Foxp3 expression and reduces the number of Treg cells in vivo. Our results are not in agreement with previous reports, which are discussed (C) 2010 Elsevier Inc All rights reserved