Adjuvant activity of tubeimosides by mediating the local immune microenvironment.
Adjuvant activity of tubeimosides by mediating the local immune microenvironment.
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DOI：
10.3389/fimmu.2023.1108244
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发表时间：
2023
影响因子：
7.3
通讯作者：
Sun, Hongxiang
中科院分区：
文献类型：
--
作者：
Han, Ziyi;Jin, Junjie;Chen, Xiangfeng;He, Yanfei;Sun, Hongxiang
关键词：
土贝母（Rhizoma Bolbostemma Paniculatum）为土贝母（Bolbostemma Paniculatum）的干燥块茎，在中医学上用于治疗急性乳腺炎和肿瘤。在这项研究中，tubeimoside（TBM）I，II，和III从这种药物的佐剂活性，构效关系（SAR），和作用机制进行了研究。三种TBMs均能显著增强小鼠对卵清蛋白（OVA）的体液和细胞免疫应答，并诱导Th 1/Th 2和Tc 1/Tc 2应答。TBM I还显著促进局部肌肉组织中各种趋化因子和细胞因子的mRNA和蛋白表达。流式细胞术显示，TBM I促进了注射肌肉中免疫细胞的募集和抗原摄取，并增强了免疫细胞向引流淋巴结的迁移和抗原转运。基因表达谱芯片分析表明，TBM I调节免疫，趋化性和炎症相关基因。网络药理学、转录组学和分子对接的综合分析预测，TBM I通过与SYK和林恩相互作用而发挥佐剂活性。进一步研究证实SYK-STAT 3信号轴参与了TBM I诱导的C2 C12细胞炎症反应。我们的研究结果首次表明，TBMs可能是有前途的疫苗佐剂候选者，并通过介导局部免疫微环境发挥佐剂活性。SAR信息有助于开发具有佐剂活性的半合成皂苷衍生物。
Rhizoma Bolbostemmatis, the dry tuber of Bolbostemma paniculatum, has being used for the treatment of acute mastitis and tumors in traditional Chinese medicine. In this study, tubeimoside (TBM) I, II, and III from this drug were investigated for the adjuvant activities, structure-activity relationships (SAR), and mechanisms of action. Three TBMs significantly boosted the antigen-specific humoral and cellular immune responses and elicited both Th1/Th2 and Tc1/Tc2 responses towards ovalbumin (OVA) in mice. TBM I also remarkably facilitated mRNA and protein expression of various chemokines and cytokines in the local muscle tissues. Flow cytometry revealed that TBM I promoted the recruitment and antigen uptake of immune cells in the injected muscles, and augmented the migration and antigen transport of immune cells to the draining lymph nodes. Gene expression microarray analysis manifested that TBM I modulated immune, chemotaxis, and inflammation-related genes. The integrated analysis of network pharmacology, transcriptomics, and molecular docking predicted that TBM I exerted adjuvant activity by interaction with SYK and LYN. Further investigation verified that SYK-STAT3 signaling axis was involved in the TBM I-induced inflammatory response in the C2C12 cells. Our results for the first time demonstrated that TBMs might be promising vaccine adjuvant candidates and exert the adjuvant activity through mediating the local immune microenvironment. SAR information contributes to developing the semisynthetic saponin derivatives with adjuvant activities.
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