In LADA patients, Tregs are reduced and FOXP3 is downregulated in CD4⁺ T cells, but the etiology remains unclear. Our study included in 20 LADA patients and 20 healthy control patients. qRT-PCR results showed that STAT3, HDAC3, HDAC5, SIRT1, DNMT1 and DNMT3b mRNAs were significantly upregulated in LADA CD4⁺ T cells than controls, while FOXP3 mRNA significantly decreased. p-STAT3, STAT3, DNMT1 and DNMT3b expressions were increased demonstrated by western blot. ChIP-PCR suggested that p-STAT3 binds to the Foxp3 promoter, meanwhile, histone H3 acetylation at K9 and K14 of FOXP3 promoter were significantly lower than controls. Luciferase reporter assay showed that ectopic STAT3 expression significantly reduced FOXP3 promoter activities. The Foxp3 promoter was significantly hypermethylated in LADA than controls. LADA patients showed stronger binding of p-STAT3, HDAC5 and DNMT1 than controls using CHIP. These findings reveal a crucial role of STAT3 in regulating the epigenetic status of T cells in LADA.

在LADA患者中，CD4 ⁺ T细胞中的Treg降低且FOXP3下调，但病因仍不清楚。我们的研究包括20名LADA患者和20名健康对照患者。qRT-PCR结果显示LADA CD4 ⁺中STAT3，HDAC3，HDAC5，SIRT1，DNMT1和DNMT3b mRNA显着上调T细胞比对照组少，而FOXP3 mRNA显着下降。Western blot证实p-STAT3，STAT3，DNMT1和DNMT3b表达增加。ChIP-PCR表明p-STAT3与Foxp3启动子结合，同时，FOXP3启动子在K9和K14处的组蛋白H3乙酰化明显低于对照组。荧光素酶报告基因测定表明，异位STAT3表达显着降低了FOXP3启动子活性。Foxp3启动子在LADA中的甲基化程度明显高于对照组。与使用CHIP的对照组相比，LADA患者显示出对p-STAT3，HDAC5和DNMT1的更强结合。这些发现揭示了STAT3在调节LADA中T细胞的表观遗传状态中的关键作用。