清肠化湿颗粒通过恢复树突状细胞介导的 Th17/Treg 平衡改善实验性结肠炎。
Qingchang Huashi granule ameliorates experimental colitis via restoring the dendritic cell-mediated Th17/Treg balance.
机构信息
Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, China.
Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, China.
出版信息
BMC Complement Med Ther. 2020 Sep 23;20(1):291. doi: 10.1186/s12906-020-03088-y.
BACKGROUND
The balance between T helper 17 (Th17) cells and regulatory T cells (Tregs) is involved in immunological tolerance. Destruction of immunological tolerance by dendritic cell (DC)-mediated T cells is involved in the pathogenesis of ulcerative colitis (UC). Qingchang Huashi granule (QCHS) has been confirmed in the treatment of UC involved by inhibiting the activation of DCs. The aim of this study was to investigate the mechanism through which QCHS restores the Th17/Treg balance by modulating DCs in the treatment of UC.
METHODS
The effects of QCHS on Th17 cells, Tregs and DCs were detected in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model. Furthermore, we injected QCHS-treated DCs into colitis model to test whether QCHS modulates the Th17/Treg balance via DCs. Tregs and Th17 cells were analyzed by FACS. IL-10, IL-17, and Foxp3 were measured by ELISA, Western blot and qRT-PCR.
RESULTS
Both QCHS and QCHS-treated DCs improved colonic histopathology, diminished Th17 cell differentiation and inhibited IL-17 production while promoting CD4CD25Foxp3 Treg differentiation and augmenting IL-10 and Foxp3 expression in colitis mice. Additionally, QCHS reduced CD86 and MHC-II expression on DCs, decreased IL-12 production ex vivo and restored the Th17/Treg ratio in the colitis model.
CONCLUSION
The findings of this study indicate that QCHS ameliorates TNBS-induced colitis by restoring the DC-mediated Th17/Treg balance.
背景
辅助性 T 细胞 17（Th17）细胞与调节性 T 细胞（Treg）之间的平衡参与免疫耐受。树突状细胞（DC）介导的 T 细胞破坏免疫耐受与溃疡性结肠炎（UC）的发病机制有关。 Qingchang Huashi 颗粒（QCHS）已被证实通过抑制 DC 的激活参与 UC 的治疗。本研究旨在探讨 QCHS 通过调节 DC 恢复 Th17/Treg 平衡从而治疗 UC 的机制。
方法
在 2,4,6-三硝基苯磺酸（TNBS）诱导的实验性结肠炎模型中检测 QCHS 对 Th17 细胞、Treg 和 DC 的影响。此外，我们将 QCHS 处理的 DC 注射到结肠炎模型中，以测试 QCHS 是否通过 DC 调节 Th17/Treg 平衡。通过 FACS 分析 Treg 和 Th17 细胞。通过 ELISA、Western blot 和 qRT-PCR 检测 IL-10、IL-17 和 Foxp3。
结果
QCHS 和 QCHS 处理的 DC 均改善了结肠组织病理学，减少了 Th17 细胞分化，抑制了 IL-17 的产生，同时促进了 CD4CD25Foxp3 Treg 的分化，并增加了结肠炎小鼠中 IL-10 和 Foxp3 的表达。此外，QCHS 降低了 DC 上的 CD86 和 MHC-II 表达，减少了体外 IL-12 的产生，并在结肠炎模型中恢复了 Th17/Treg 比值。
结论
本研究结果表明，QCHS 通过恢复 DC 介导的 Th17/Treg 平衡来改善 TNBS 诱导的结肠炎。
Zotero 插件