Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Immunol. 2022 Feb 11;13:851560. doi: 10.3389/fimmu.2022.851560. eCollection 2022.
Autoimmune hepatitis (AIH) is characterized by chronic progressive liver inflammatory, but there is still no safe and effective medicine. Therefore, glucocorticoid remains the top choice for AIH treatment. In previous studies, it has been confirmed that ginsenosides (GSS) can produce glucocorticoid-like effects and therapeutic effects on various autoimmune diseases. However, the mechanism of GSS for AIH remains unclear. As an important part of the innate immune system, bone marrow-derived suppressor cells (MDSC) have been identified as an important driver of follow-up acquired immune response in many autoimmune diseases, including AIH. Herein, it was found out that GSS intervention can be effective in regulating the immune microenvironment and liver impairment induced by Con A in AIH mice. , the MDSCs derived from healthy mice and the T cells deried from AIH mice were co-cultured. Then, different drugs were intervened with to explore the therapeutic mechanism. Besides, the proliferation and differentiation of MDSCs and T cells were analyzed by flow cytometry, while GR, Hippo-YAP signal pathway and the expression of MDSC-related genes and proteins were detected through qRT-PCR and Western Blot. The changes in NO and ROS levels were further analyzed. The trend of related cytokines expression (IFN- γ, TGF- β, IL-10, IL-6, IL-17) was detected by ELISA. Furthermore, an analysis was conducted as to the ALT and liver pathology of mice for evaluating the liver function of mice. It was discovered that MDSCs proliferation was inhibited, and that T cells tended to differentiate into Th17 rather than Treg in AIH mice. Moreover, the intervention of GSS activated GR and Yap, in addition to promoting the proliferation of MDSCs, especially M-MDSCs. This further promoted the differentiation of Treg to enable immune tolerance, thus alleviating liver impairment. Therefore, it was proposed that GSS can alleviate AIH by modulating the innate immunity and adaptive T cell immunity, which may be the underlying mechanism for GSS to mitigate the liver impairment induced by AIH.
自身免疫性肝炎（AIH）的特征是慢性进行性肝脏炎症，但目前仍然没有安全有效的药物。因此，糖皮质激素仍然是 AIH 治疗的首选。在以前的研究中，已经证实人参皂苷（GSS）可以产生类似糖皮质激素的作用，并对各种自身免疫性疾病产生治疗作用。然而，GSS 治疗 AIH 的机制尚不清楚。骨髓来源的抑制细胞（MDSC）作为先天免疫系统的重要组成部分，已被确定为包括 AIH 在内的许多自身免疫性疾病中后续获得性免疫反应的重要驱动因素。在此，研究人员发现 GSS 干预可以有效调节 AIH 小鼠中 ConA 诱导的免疫微环境和肝损伤。将来自健康小鼠的 MDSC 和来自 AIH 小鼠的 T 细胞进行共培养。然后，用不同的药物进行干预，以探讨其治疗机制。此外，通过流式细胞术分析 MDSC 和 T 细胞的增殖和分化，通过 qRT-PCR 和 Western Blot 检测 MDSC 相关基因和蛋白的表达。进一步分析 NO 和 ROS 水平的变化。通过 ELISA 检测相关细胞因子表达（IFN-γ、TGF-β、IL-10、IL-6、IL-17）的变化趋势。进一步评估小鼠 ALT 和肝病理变化，以评价小鼠肝功能。结果发现，AIH 小鼠 MDSC 增殖受到抑制，T 细胞倾向于向 Th17 分化而不是 Treg 分化。此外，GSS 的干预激活了 GR 和 Yap，除了促进 MDSC 增殖外，尤其是 M-MDSC。这进一步促进了 Treg 的分化，从而产生免疫耐受，从而缓解肝损伤。因此，研究人员提出，GSS 通过调节固有免疫和适应性 T 细胞免疫来缓解 AIH，这可能是 GSS 缓解 AIH 诱导的肝损伤的潜在机制。
