In our previous studies, we found that extracellular vesicles in mesenchymal stem cells can alleviate ulcerative colitis. In view of the fact that extracellular vesicles have the same immunomodulatory effects as their maternal cells and considering the important role of Th17 cells in the pathogenesis of ulcerative colitis, we aimed to investigate whether extracellular vesicles from mesenchymal stem cells can affect the differentiation of Th17 cells in ulcerative colitis. Histone H3K27me3 can regulate the expression of Th17 cell-related genes. We focused on determining whether the effect of extracellular vesicles on Th17 cells in ulcerative colitis is related to H3K27me3. For our experiments, we used low, medium and high doses of extracellular vesicles from mesenchymal stem cells to interfere with TNBS-induced colitis in rats and then evaluated the alleviation of inflammation and observed the impact of the extracellular vesicles on the differentiation of Th17 cells in ulcerative colitis. In addition, we detected the levels of histone H3K27me3 and the expression of its upstream methyltransferase and demethylase in the colon tissues of each group. Our data showed that extracellular vesicles from bone marrow mesenchymal stem cells can inhibit the abnormal differentiation of Th17 cells in ulcerative colitis, and the content of histone H3K27me3 was also changed accordingly. Our study suggests that extracellular vesicles from mesenchymal stem cells could inhibit the differentiation of Th17 cells in ulcerative colitis by regulating H3K27me3. This study reveals that H3K27me3 is an important target for inflammatory immune diseases associated with abnormal Th17 cell differentiation and indicates that mesenchymal stem cell extracellular vesicles are promising agents for the treatment of ulcerative colitis.

中文翻译：

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BMSC-EVs通过H3K27me3调节UC中Th17细胞的分化。

在我们以前的研究中，我们发现间充质干细胞中的细胞外囊泡可以减轻溃疡性结肠炎。鉴于细胞外囊泡与母体细胞具有相同的免疫调节作用，并考虑到Th17细胞在溃疡性结肠炎发病机理中的重要作用，我们旨在研究间充质干细胞的细胞外囊泡是否会影响Th17细胞的分化在溃疡性结肠炎中。组蛋白H3K27me3可以调节Th17细胞相关基因的表达。我们集中于确定溃疡性结肠炎中细胞外囊泡对Th17细胞的作用是否与H3K27me3有关。在我们的实验中，我们使用了低 中量和高剂量的间充质干细胞胞外小泡干扰TNBS诱导的大鼠结肠炎，然后评估炎症缓解程度，并观察胞外小泡对溃疡性结肠炎Th17细胞分化的影响。此外，我们检测了每组结肠组织中组蛋白H3K27me3的水平及其上游甲基转移酶和脱甲基酶的表达。我们的数据表明，来自骨髓间充质干细胞的细胞外囊泡可以抑制溃疡性结肠炎中Th17细胞的异常分化，并且组蛋白H3K27me3的含量也发生了变化。我们的研究表明，间充质干细胞的细胞外囊泡可通过调节H3K27me3抑制溃疡性结肠炎Th17细胞的分化。