The induction of immune tolerance and the improvement islet transplantation with histone deacetylase inhibitors.

我们将重点放在组蛋白脱乙酰酶抑制剂(HDACi)上，因为据报道，抑制HDAC活性会阻止Treg分化为产生IL17的细胞。因此，我们试图增强Treg，同时抑制Th17细胞，使用DST和HDACi来延长移植物存活。为了用DST刺激Treg，我们使用了供体脾细胞。DST+HDACi组胸腺和脾Foxp3基因表达增加，Treg细胞数增加，Th17细胞数减少。淋巴细胞mRNA定量聚合酶链式反应分析显示，Foxp3、IL-10和转化生长因子-β的表达增加。而DST+HDACi组IL-17a、STAT3(Th17)和干扰素-g的表达较单独DST组降低。此外，在小鼠胰岛移植中，与对照组相比，经HDACi处理的DST可延长移植物存活时间。因此，DST+HDACi在胰岛移植中可能有一定的应用价值。

We focused on histone deacetylase inhibitors (HDACi) because it was reported that inhibition of HDAC activity prevented Treg differentiation into IL17-producing cells. We therefore sought to enhance Treg while suppressing Th17 cells using DST with HDACi to prolong graft survival. To stimulate Treg by DST, we used donor splenocytes. In DST with HDACi group, Foxp3 mRNA expression and Treg population increased in the thymus and spleen, whereas Th17 population decreased. qPCR analysis of lymphocyte mRNA indicated that Foxp3, IL-10, and TGF-b expression increased. However, interleukin 17a, Stat3 (Th17), and IFN-g expression decreased in DST + HDACi group, relative to DST alone. Moreover, DST treated with HDACi prolonged graft survival relative to controls in mice islet transplantation. DST with HDACi may therefore have utility in islet transplantation.