Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China.
Mol Immunol. 2020 Feb;118:191-200. doi: 10.1016/j.molimm.2019.12.019. Epub 2019 Dec 30.
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.
在我们之前的研究中，我们发现间充质干细胞的细胞外囊泡可以缓解溃疡性结肠炎。鉴于细胞外囊泡具有与其母细胞相同的免疫调节作用，并且考虑到 Th17 细胞在溃疡性结肠炎发病机制中的重要作用，我们旨在研究间充质干细胞的细胞外囊泡是否可以影响溃疡性结肠炎中 Th17 细胞的分化。组蛋白 H3K27me3 可以调节 Th17 细胞相关基因的表达。我们专注于确定细胞外囊泡对溃疡性结肠炎中 Th17 细胞的影响是否与 H3K27me3 有关。在我们的实验中，我们使用低、中、高剂量的间充质干细胞细胞外囊泡来干扰 TNBS 诱导的大鼠结肠炎，然后评估炎症的缓解情况，并观察细胞外囊泡对溃疡性结肠炎中 Th17 细胞分化的影响。此外，我们检测了各组结肠组织中组蛋白 H3K27me3 及其上游甲基转移酶和去甲基化酶的水平。我们的数据表明，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，组蛋白 H3K27me3 的含量也相应发生变化。我们的研究表明，间充质干细胞的细胞外囊泡可以通过调节 H3K27me3 来抑制溃疡性结肠炎中 Th17 细胞的分化。这项研究表明，H3K27me3 是与异常 Th17 细胞分化相关的炎症性免疫疾病的一个重要靶点，并表明间充质干细胞细胞外囊泡是治疗溃疡性结肠炎的有前途的药物。
