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目的分析组蛋白去乙酰化酶6抑制剂(HDAC6i)tubacin在体外对调节性T细胞(Treg)的叉状头转录因子3(Foxp3)表达的影响,并鉴定经tubacin处理后的Treg的免疫生物学特性。方法用磁珠双阳性分选的方法从C57BL/6J小鼠脾脏细胞中获得CD4+CD25+T细胞和CD4+CD25-T细胞,应用tubacin对天然型Treg(n Treg)及转化生长因子β1(TGF-β1)诱导分化的诱导型Treg(i Treg)进行诱导培育,鉴定各群细胞Foxp3的表达状况,并通过混合淋巴细胞培养(MLC)实验分析各群细胞的免疫抑制活性及相关机制。结果小鼠n Treg及i Treg经tubacin孵化后Foxp3表达均明显增强,通过MLC实验证实,n Treg及i Treg经tubacin培养诱导后可获得更强的免疫抑制活性,能显著抑制同基因CD4+CD25-T细胞的活化。结论组蛋白去乙酰化酶6抑制剂tubacin可上调CD4+CD25+Treg的Foxp3表达,并增强其细胞免疫抑制活性。
Objective To analyze the effect of histone deacetylase 6 inhibitor (HDAC6i) tubacin on the expression of forkhead transcription factor 3 (Foxp3) of regulatory T cells (Tregs) in vitro and to identify the immunological organisms of Tregs treated with tubacin Learn characteristics. Methods CD4 + CD25 + T cells and CD4 + CD25-T cells were obtained from the spleen cells of C57BL / 6J mice by double positive magnetic bead sorting. Tubacin was used to detect the expression of natural Treg (n Treg) and transforming growth factor β1 TGF-β1) -induced induction of Treg (i Treg) were induced and cultured to identify the expression of Foxp3 in each group of cells. MLC assay was used to analyze the immunosuppressive activity of each group of cells and its related mechanism. Results Foxp3 expression was significantly enhanced after tubercin incubation in nTreg and iTregs. MLC assay showed that nTreg and iTreg induced stronger immunosuppressive activity induced by tubacin and significantly inhibited the increase of CD4 + CD25 -T cell activation. Conclusion tubacin, a histone deacetylase 6 inhibitor, can up-regulate the Foxp3 expression of CD4 + CD25 + Treg and enhance its immunosuppressive activity.