组蛋白去乙酰化酶抑制剂的免疫抑制功能研究进展

Immunosuppressive function of histone deacetylases inhibitors:recent progress

组蛋白去乙酰化酶抑制剂(histone deacetylases inhibitors,HDACIs)是一类在转录水平调控基因表达的化合物,通过诱导蛋白过乙酰化引起染色体重建、细胞周期停滞、诱导细胞分化和凋亡以及调节转录因子活化和抑制等一系列生物学效应。HDACIs在多种血液系统肿瘤和实体瘤中显示了明确而强大的抗肿瘤活性,目前已进入临床研究阶段。其在炎症免疫疾病动物模型及基础研究中显示出的免疫抑制活性,为探索从基因水平治疗炎症免疫性疾病及移植术后排斥反应带来了新思路。本文从炎症免疫性疾病、T淋巴细胞、促炎细胞因子及树突状细胞(dendritic cells,DCs)功能等几方面,对HDACIs参与的免疫调节功能研究进展作一综述。

Histone deacetylases inhibitors（HDACIs）are a group of compound regulating gene expression at transcriptional level.HDACIs can induce protein hyperacetylation and subsequently lead to chromatin remodeling,cell-cycle arrest,cell differentiation and apoptosis,and transcriptional activation and repression.HDACIs demonstrate promising antitumor activity and are presently tested in clinical studies for solid and hematologic malignancies.Cumulating evidence in animal models of immune disorders also suggests immunosuppressive properties of HDACIs,which provides us with new ideas for treating immune disorders and rejection after transplantation.This paper reviews the recent progress of immunosuppressive function induced by HDACIs from the following aspects：immune diseases,T lymphocytes,inflammatory cytokines and dendritic cells.