Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104-4318, USA.
Clin Immunol. 2010 Sep;136(3):348-63. doi: 10.1016/j.clim.2010.04.018. Epub 2010 May 15.
Histone/protein deacetylases (HDACs) decrease histone and protein acetylation, typically leading to suppression of gene transcription and modulation of various protein functions. We found significant differences in expression of HDAC before and after stimulation of human T regulatory (Treg) and T effector cells, suggesting the potential for future selective targeting of Tregs with HDAC inhibitors (HDACi). Use of various HDACi small molecules enhanced, by up to 4.5-fold (average 2-fold), the suppressive functions of both freshly isolated and expanded human Tregs, consistent with our previous murine data. HDACi use increased Treg expression of CTLA-4, a key negative regulator of immune response, and we found a direct and significant correlation between CTLA-4 expression and Treg suppression. Hence, HDACi compounds are promising pharmacologic tools to increase Treg suppressive functions, and this action may potentially be of use in patients with autoimmunity or post-transplantation.
组蛋白/蛋白质去乙酰化酶（HDACs）可降低组蛋白和蛋白质的乙酰化水平，通常导致基因转录的抑制和各种蛋白质功能的调节。我们发现人类调节性 T 细胞（Treg）和效应 T 细胞刺激前后 HDAC 的表达存在显著差异，这表明将来有可能使用 HDAC 抑制剂（HDACi）对 Tregs 进行选择性靶向治疗。使用各种 HDACi 小分子可将新鲜分离和扩增的人类 Treg 的抑制功能增强多达 4.5 倍（平均 2 倍），这与我们之前的鼠类数据一致。HDACi 的使用增加了 CTLA-4 的表达，CTLA-4 是免疫反应的关键负调节剂，我们发现 CTLA-4 表达与 Treg 抑制之间存在直接且显著的相关性。因此，HDACi 化合物是增加 Treg 抑制功能的有前途的药物工具，并且这种作用在自身免疫或移植后患者中可能有用。
