薯蓣皂苷通过IL-4R相关的上皮-免疫反应调节减轻过敏性气道炎症
2026/06/30
摘要
背景：过敏性哮喘以气道炎症、上皮屏障功能障碍和免疫反应失调为特征。尽管Th2细胞因子和白细胞介素-4受体（IL-4R）信号通路是其发病机制的核心，但越来越多的证据表明，上皮-免疫相互作用、代谢紊乱以及肠-肺轴失调也参与其中。薯蓣皂苷是一种天然甾体皂苷，已显示出抗炎特性，但其在气道炎症中的作用尚未得到充分研究。
方法：建立卵清蛋白（OVA）诱导的BALB/c小鼠哮喘模型，评估薯蓣皂苷对气道功能、上皮完整性、免疫细胞分布和黏膜炎症的影响。采用肺组织代谢组学和16S rRNA基因测序评估代谢谱及微生物群特征。体外建立两种共培养模型：采用骨髓来源树突状细胞（BMDC）-BEAS-2B共培养模型评估IL-4R调控条件下的上皮-免疫串扰；采用BMDC-RBL-2H3共培养模型，在IL-4R表达改变的情况下，评估LPS/IL-4刺激下肥大细胞相关的免疫反应。
结果：薯蓣皂苷给药与气道高反应性、炎症细胞浸润、氧化应激及Th2/Th17相关细胞因子水平降低相关。肺组织代谢组学显示，薯蓣皂苷可部分纠正OVA诱导的代谢失衡，尤其是谷胱甘肽和嘌呤代谢通路的异常。16S rRNA测序显示，微生物群多样性和组成得到部分恢复。免疫特征分析显示，CD86+/CD206+免疫细胞表型比值发生改变，嗜酸性粒细胞和CD4+IL-4+ T细胞浸润减少。在BEAS-2B共培养体系中，IL-4R表达可调节上皮细胞对炎症刺激和薯蓣皂苷的反应。此外，RBL-2H3体系可用于评估肥大细胞脱颗粒和FcεRI相关信号通路，而这些过程同样受到IL-4R水平的影响。
结论：本研究表明，薯蓣皂苷可减轻过敏性气道炎症，并与上皮完整性改善、氧化应激降低及免疫失调减轻相关。体外共培养实验提示，IL-4R表达可调节上皮-免疫反应的强度；然而，现有数据尚不能证实体内存在直接依赖IL-4R的作用机制。代谢组学和微生物群结果应被视为探索性的系统层面关联，而非确证性的机制证据。这些发现为过敏性气道疾病的黏膜免疫调节及基于天然化合物的干预提供了新的认识。
Dioscin alleviates allergic airway inflammation with IL-4R-associated modulation of epithelial-immune responses
Chunxue Meng, Changbin Zhao, Qianxi Na, Qian Zhang, Fei Wang, Jing Zhang, Xuhong Tang, Zihua Chen, Guangbin Wang, Dong Liu, Kun Zhang, Bin Guo
Abstract
BACKGROUND:Allergic asthma is characterized by airway inflammation, epithelial barrier dysfunction, and dysregulated immune responses. While Th2 cytokines and IL-4 receptor (IL-4R) signaling are central to its pathogenesis, accumulating evidence underscores the involvement of epithelial-immune interactions, metabolic disturbances, and gut-lung axis dysregulation. Dioscin, a natural steroidal saponin, has demonstrated anti-inflammatory properties, but its role in airway inflammation remains insufficiently explored.
METHODS:We established an ovalbumin (OVA)-induced asthma model in BALB/c mice to assess the effects of dioscin on airway function, epithelial integrity, immune cell distribution, and mucosal inflammation. Lung metabolomics and 16S rRNA gene sequencing were conducted to evaluate metabolic and microbiota profiles. In vitro, two co-culture models were established: BMDCs-BEAS-2B to evaluate epithelial-immune crosstalk under IL-4R modulation, and BMDCs-RBL-2H3 to assess mast cell-associated immune responses under LPS/IL-4 stimulation with altered IL-4R expression.
RESULTS:Dioscin administration was associated with reduced airway hyperresponsiveness, inflammatory infiltration, oxidative stress, and Th2/Th17-related cytokine levels. Lung metabolomics revealed that dioscin partially restored OVA-induced metabolic imbalances, particularly in glutathione and purine metabolism pathways. 16S rRNA sequencing showed a partial recovery of microbial diversity and composition. Immune profiling indicated a shift in CD86+/CD206+ immune-cell phenotype ratio and reduced eosinophil and CD4+IL-4+ T cell infiltration. In BEAS-2B co-cultures, IL-4R expression modulated epithelial responsiveness to inflammatory cues and dioscin. In addition, the RBL-2H3 system allowed the evaluation of mast cell degranulation and FcεRI-related signaling, which were also influenced by IL-4R levels.
CONCLUSION:This study shows that dioscin alleviates allergic airway inflammation and is associated with improved epithelial integrity, reduced oxidative stress, and attenuated immune dysregulation. In vitro co-culture experiments suggest that IL-4R expression modulates the magnitude of epithelial-immune responses, but the current data do not establish a direct IL-4R-dependent mechanism in vivo; the metabolomic and microbiota findings should be interpreted as exploratory system-level associations rather than definitive mechanistic evidence. These findings provide insights into mucosal immunoregulation and natural compound-based interventions for allergic airway disease.
背景：过敏性哮喘以气道炎症、上皮屏障功能障碍和免疫反应失调为特征。尽管Th2细胞因子和白细胞介素-4受体（IL-4R）信号通路是其发病机制的核心，但越来越多的证据表明，上皮-免疫相互作用、代谢紊乱以及肠-肺轴失调也参与其中。薯蓣皂苷是一种天然甾体皂苷，已显示出抗炎特性，但其在气道炎症中的作用尚未得到充分研究。
方法：建立卵清蛋白（OVA）诱导的BALB/c小鼠哮喘模型，评估薯蓣皂苷对气道功能、上皮完整性、免疫细胞分布和黏膜炎症的影响。采用肺组织代谢组学和16S rRNA基因测序评估代谢谱及微生物群特征。体外建立两种共培养模型：采用骨髓来源树突状细胞（BMDC）-BEAS-2B共培养模型评估IL-4R调控条件下的上皮-免疫串扰；采用BMDC-RBL-2H3共培养模型，在IL-4R表达改变的情况下，评估LPS/IL-4刺激下肥大细胞相关的免疫反应。
结果：薯蓣皂苷给药与气道高反应性、炎症细胞浸润、氧化应激及Th2/Th17相关细胞因子水平降低相关。肺组织代谢组学显示，薯蓣皂苷可部分纠正OVA诱导的代谢失衡，尤其是谷胱甘肽和嘌呤代谢通路的异常。16S rRNA测序显示，微生物群多样性和组成得到部分恢复。免疫特征分析显示，CD86+/CD206+免疫细胞表型比值发生改变，嗜酸性粒细胞和CD4+IL-4+ T细胞浸润减少。在BEAS-2B共培养体系中，IL-4R表达可调节上皮细胞对炎症刺激和薯蓣皂苷的反应。此外，RBL-2H3体系可用于评估肥大细胞脱颗粒和FcεRI相关信号通路，而这些过程同样受到IL-4R水平的影响。
结论：本研究表明，薯蓣皂苷可减轻过敏性气道炎症，并与上皮完整性改善、氧化应激降低及免疫失调减轻相关。体外共培养实验提示，IL-4R表达可调节上皮-免疫反应的强度；然而，现有数据尚不能证实体内存在直接依赖IL-4R的作用机制。代谢组学和微生物群结果应被视为探索性的系统层面关联，而非确证性的机制证据。这些发现为过敏性气道疾病的黏膜免疫调节及基于天然化合物的干预提供了新的认识。
（中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校）
（Int Immunopharmacol. 2026 Sep;184:116890. DOI: https://doi.org/10.1016/j.intimp.2026.116890）
（Int Immunopharmacol. 2026 Sep;184:116890. DOI: https://doi.org/10.1016/j.intimp.2026.116890）
Dioscin alleviates allergic airway inflammation with IL-4R-associated modulation of epithelial-immune responses
Chunxue Meng, Changbin Zhao, Qianxi Na, Qian Zhang, Fei Wang, Jing Zhang, Xuhong Tang, Zihua Chen, Guangbin Wang, Dong Liu, Kun Zhang, Bin Guo
Abstract
BACKGROUND:Allergic asthma is characterized by airway inflammation, epithelial barrier dysfunction, and dysregulated immune responses. While Th2 cytokines and IL-4 receptor (IL-4R) signaling are central to its pathogenesis, accumulating evidence underscores the involvement of epithelial-immune interactions, metabolic disturbances, and gut-lung axis dysregulation. Dioscin, a natural steroidal saponin, has demonstrated anti-inflammatory properties, but its role in airway inflammation remains insufficiently explored.
METHODS:We established an ovalbumin (OVA)-induced asthma model in BALB/c mice to assess the effects of dioscin on airway function, epithelial integrity, immune cell distribution, and mucosal inflammation. Lung metabolomics and 16S rRNA gene sequencing were conducted to evaluate metabolic and microbiota profiles. In vitro, two co-culture models were established: BMDCs-BEAS-2B to evaluate epithelial-immune crosstalk under IL-4R modulation, and BMDCs-RBL-2H3 to assess mast cell-associated immune responses under LPS/IL-4 stimulation with altered IL-4R expression.
RESULTS:Dioscin administration was associated with reduced airway hyperresponsiveness, inflammatory infiltration, oxidative stress, and Th2/Th17-related cytokine levels. Lung metabolomics revealed that dioscin partially restored OVA-induced metabolic imbalances, particularly in glutathione and purine metabolism pathways. 16S rRNA sequencing showed a partial recovery of microbial diversity and composition. Immune profiling indicated a shift in CD86+/CD206+ immune-cell phenotype ratio and reduced eosinophil and CD4+IL-4+ T cell infiltration. In BEAS-2B co-cultures, IL-4R expression modulated epithelial responsiveness to inflammatory cues and dioscin. In addition, the RBL-2H3 system allowed the evaluation of mast cell degranulation and FcεRI-related signaling, which were also influenced by IL-4R levels.
CONCLUSION:This study shows that dioscin alleviates allergic airway inflammation and is associated with improved epithelial integrity, reduced oxidative stress, and attenuated immune dysregulation. In vitro co-culture experiments suggest that IL-4R expression modulates the magnitude of epithelial-immune responses, but the current data do not establish a direct IL-4R-dependent mechanism in vivo; the metabolomic and microbiota findings should be interpreted as exploratory system-level associations rather than definitive mechanistic evidence. These findings provide insights into mucosal immunoregulation and natural compound-based interventions for allergic airway disease.
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多组分免疫营养补充剂用于过敏性哮喘和鼻炎患儿的探索性先导试验：INAPRA研究
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