Histone Deacetylase 3 Is Required for Efficient T Cell Development
Histone Deacetylase 3 Is Required for Efficient T Cell Development
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DOI：
10.1128/mcb.00706-15
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发表时间：
2015-08
影响因子：
5.3
通讯作者：
K. Stengel;Yue Zhao;Nicholas J. Klus;Jonathan F Kaiser;Laura E. Gordy;S. Joyce;S. Hiebert;Alyssa R Summers
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文献类型：
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作者：
K. Stengel;Yue Zhao;Nicholas J. Klus;Jonathan F Kaiser;Laura E. Gordy;S. Joyce;S. Hiebert;Alyssa R Summers
摘要HDAC3是在皮肤T细胞淋巴瘤中有效的HDAC抑制剂的关键靶标HDAC3在T细胞发育过程中控制的表型使用LCK-CRE转化有条件地删除了HDAC3。当HDAC3 - / - 小鼠与Bcl-XL-，BCL2-或TCRβ表达的转基因小鼠时，产生的CD4/CD8双阳性阶段几乎没有成熟的CD4+或CD8+单阳性细胞。但是，当将无效的小鼠与表达完全重排的T细胞受体αβ转基因的小鼠交叉时，会产生正常的CD4单阳性细胞。通过积极的选择。
ABSTRACT Hdac3 is a key target for Hdac inhibitors that are efficacious in cutaneous T cell lymphoma. Moreover, the regulation of chromatin structure is critical as thymocytes transition from an immature cell with open chromatin to a mature T cell with tightly condensed chromatin. To define the phenotypes controlled by Hdac3 during T cell development, we conditionally deleted Hdac3 using the Lck-Cre transgene. This strategy inactivated Hdac3 in the double-negative stages of thymocyte development and caused a significant impairment at the CD8 immature single-positive (ISP) stage and the CD4/CD8 double-positive stage, with few mature CD4+ or CD8+ single-positive cells being produced. When Hdac3−/− mice were crossed with Bcl-xL-, Bcl2-, or TCRβ-expressing transgenic mice, a modest level of complementation was found. However, when the null mice were crossed with mice expressing a fully rearranged T cell receptor αβ transgene, normal levels of CD4 single-positive cells were produced. Thus, Hdac3 is required for the efficient transit from double-negative stage 4 through positive selection.