Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function
Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function
复制标题
DOI：
10.1182/blood-2006-04-019711
复制
发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Huang, Qian
中科院分区：
文献类型：
--
作者：
Brogdon, Jennifer L.;Xu, Yongyao;Huang, Qian
组蛋白去乙酰化酶（HDAC）在调节基因表达和关键生物学过程中起关键作用。然而，HDAC如何参与先天免疫却知之甚少。在这里，在对HDAC在免疫中的作用的首次系统研究中，我们表明，通过小分子HDAC抑制剂（HDACI）LAQ824抑制HDAC，改变了巨噬细胞和树突状细胞（DC）的Toll样受体4（TLR4）依赖性活化和功能。令人惊讶的是，泛HDAC抑制仅调节参与免疫应答的不同分支的有限的一组基因。具体而言，它抑制DC控制的辅助性T细胞1（Th1）效应细胞，但不抑制Th2效应细胞的活化和迁移。它也抑制巨噬细胞和DC介导的单核细胞，但不中性粒细胞的趋化性。这些意想不到的发现证明了HDAC抑制在调节先天性和适应性免疫应答中的高度特异性，并突出了HDACi在治疗环境中改变Th1和Th2平衡的潜力。
Histone deacetylases (HDACs) play a critical role in regulating gene expression and key biological processes. However, how HDACs are involved in innate immunity is little understood. Here, in this first systematic investigation of the role of HDACs in immunity, we show that HDAC inhibition by a small-molecule HDAC inhibitor (HDACI), LAQ824, alters Toll-like receptor 4 (TLR4)-dependent activation and function of macrophages and dendritic cells (DCs). Surprisingly, pan-HDAC inhibition modulates only a limited set of genes involved in distinct arms of immune responses. Specifically, it inhibited DC-controlled T helper 1 (Th1) effector but not Th2 effector cell activation and migration. It also inhibited macrophage and DC-mediated monocyte but not neutrophil chemotaxis. These unexpected findings demonstrate the high specificity of HDAC inhibition in modulating innate and adaptive immune responses, and highlight the potential for HDACi to alter the Th1 and Th2 balance in therapeutic settings.