Grabiec Aleksander M, Tak Paul P, Reedquist Kris A
Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Room K0-140, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Crit Rev Immunol. 2011;31(3):233-63. doi: 10.1615/critrevimmunol.v31.i3.40.
Histone deacetylases (HDACs) display multi-faceted roles in coordinating the interaction of intracellular signaling pathways with chromatin remodeling and transcription factor function to finely specify gene alterations and maintenance of gene expression during cellular activation, proliferation, and differentiation. These processes, epigenetic and non-epigenetic, are critical to the development of both the adaptive and innate arms of the mammalian immune system, and the measured initiation and resolution of immune responses. Pharmacological modulators of HDAC activity have demonstrated uniformly potent anti-inflammatory effects in experimental animal models of these diseases, in relevant immune and stromal cell populations from patients, as well as initial successes in the clinic. Recent studies have identified key roles for specific HDACs in regulating immune function, as well as alterations in HDAC expression and function in a number of immune-mediated inflammatory diseases (IMIDs), which may contribute to pathology in these diseases. Here, we review recent advances in our understanding of HDAC function in the immune system, their contribution to IMIDs, and the therapeutic potential of altering HDAC activity in IMIDs.
组蛋白去乙酰化酶（HDACs）在协调细胞内信号通路与染色质重塑及转录因子功能的相互作用方面发挥着多方面作用，从而在细胞激活、增殖和分化过程中精确确定基因改变并维持基因表达。这些表观遗传和非表观遗传过程对于哺乳动物免疫系统适应性和先天性分支的发育以及免疫反应的适度启动和消退至关重要。HDAC活性的药理调节剂在这些疾病的实验动物模型、患者相关免疫和基质细胞群体中均显示出一致的强效抗炎作用，并且在临床上也取得了初步成功。最近的研究已经确定了特定HDACs在调节免疫功能中的关键作用，以及在多种免疫介导的炎症性疾病（IMIDs）中HDAC表达和功能的改变，这可能导致这些疾病的病理变化。在此，我们综述了我们对HDAC在免疫系统中的功能、它们对IMIDs的贡献以及改变IMIDs中HDAC活性的治疗潜力的最新认识进展。
