State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Oncology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
Phytomedicine. 2024 Oct;133:155586. doi: 10.1016/j.phymed.2024.155586. Epub 2024 Apr 2.
Autoimmune hepatitis (AIH) is characterized by persistent liver inflammation induced by aberrant immune responses. Glycyrrhizic acid (GA), a prominent bioactive ingredient of licorice, has shown potential as a safe and effective treatment for AIH. However, the immune regulatory mechanism by which GA exerts its therapeutic effect on AIH remains elusive. In this study, we found that GA intervention significantly alleviated ConA-induced acute liver injury in mice. Cytometry by time-of-flight (CyTOF) analysis revealed that GA increased the abundance of anti-inflammatory F4/80CD11bMHCII MoMF-1 and decreased the abundance of pro-inflammatory F4/80CD11biNOS MoMF-3. Multiplex immunofluorescence demonstrated the infiltration of MoMFs in liver tissues. Single-cell RNA sequencing (scRNA-seq) analysis indicated that GA facilitated the immune activation in MoMFs, regulated gene expression of diverse cytokines secreted by MoMFs, and played a role in shaping the immune microenvironment. By integrating the results of CyTOF with scRNA-seq, our study comprehensively elucidates the immune landscape of ConA-induced liver injury following GA intervention, advancing the understanding of GA's mechanism of action. However, it is important to note that some single-cell data in this study remain raw and require further processing and annotation. Our findings suggest that GA alleviates ConA-induced acute liver injury by regulating the function of MoMFs, opening potential avenues for AIH treatment and management, and providing a theoretical basis for the design of novel MoMFs-centered immunotherapies.
自身免疫性肝炎 (AIH) 的特征是异常免疫反应引起的持续肝脏炎症。甘草酸 (GA) 是甘草中的一种主要生物活性成分，已显示出作为 AIH 安全有效治疗方法的潜力。然而，GA 发挥其治疗 AIH 作用的免疫调节机制仍不清楚。在这项研究中，我们发现 GA 干预显著缓解了 ConA 诱导的小鼠急性肝损伤。飞行时间（CyTOF）分析显示，GA 增加了抗炎性 F4/80CD11bMHCII MoMF-1 的丰度，降低了促炎性 F4/80CD11biNOS MoMF-3 的丰度。多重免疫荧光显示 MoMFs 在肝组织中的浸润。单细胞 RNA 测序（scRNA-seq）分析表明，GA 促进了 MoMFs 的免疫激活，调节了 MoMFs 分泌的多种细胞因子的基因表达，并在塑造免疫微环境中发挥作用。通过将 CyTOF 的结果与 scRNA-seq 相结合，我们的研究全面阐明了 GA 干预后 ConA 诱导的肝损伤的免疫景观，深入了解了 GA 的作用机制。然而，需要注意的是，本研究中的一些单细胞数据仍为原始数据，需要进一步处理和注释。我们的研究结果表明，GA 通过调节 MoMFs 的功能缓解 ConA 诱导的急性肝损伤，为 AIH 的治疗和管理开辟了新的途径，并为设计以 MoMFs 为中心的新型免疫疗法提供了理论依据。
