农场灰尘提取物在嗜酸性粒细胞炎症小鼠模型中的治疗潜力
2025/10/31
摘要
背景：哮喘影响全球超过3.55亿人，并构成重大的医疗负担。虽然皮质类固醇仍是治疗的基石，但其副作用凸显了对额外治疗策略的需求。传统农场灰尘等环境暴露已被证实与预防哮喘和过敏相关。本研究通过在致敏后及过敏原激发期间（模拟二级预防或早期干预治疗策略）施用农场灰尘提取物（FDE）来探讨FDE在过敏性哮喘小鼠模型中的治疗潜力。
方法：我们采用卵清蛋白（OVA）诱导的哮喘模型来评估FDE对气道嗜酸性粒细胞增多、气道高反应性（AHR）、黏液产生及IgE水平的影响。机制研究评估了调节性T细胞（Tregs）、树突状细胞表型、上皮屏障完整性及细胞因子信号传导。在哮喘患者的外周血单个核细胞（PBMCs）中进行了补充实验。
结果：FDE显著减轻了气道炎症和AHR，二级预防效果与全身地塞米松相当。FDE增强了Treg频率和CTLA-4表达，调节树突状细胞的MHC-II和PD-L1表达，并促进了免疫调节环境。它还恢复了上皮屏障完整性并增加了IL-33的释放，从而支持Treg的激活。在哮喘患者的PBMCs中，FDE增加了Treg，减少了Th2细胞，并抑制了CIITA，表明了类似的免疫调节作用。IL-33、双调蛋白（AREG）和Treg之间的相互作用揭示了一个强化免疫－上皮稳态的机制。
结论：在致敏后及过敏原激发期间施用FDE，能够减轻小鼠的关键哮喘特征，并在人类细胞中显示出转化潜力，这支持了将其作为一种新型的、源于环境的免疫调节策略进行开发。
The Therapeutic Potential of Farm Dust Extracts in a Mouse Model of Eosinophilic Inflammation.
Rabia Ülkü, Korkmaz; Jimmy,
BACKGROUND: Asthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach.
METHODS: We used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors.
RESULTS: FDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis.
CONCLUSION: FDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy.
背景：哮喘影响全球超过3.55亿人，并构成重大的医疗负担。虽然皮质类固醇仍是治疗的基石，但其副作用凸显了对额外治疗策略的需求。传统农场灰尘等环境暴露已被证实与预防哮喘和过敏相关。本研究通过在致敏后及过敏原激发期间（模拟二级预防或早期干预治疗策略）施用农场灰尘提取物（FDE）来探讨FDE在过敏性哮喘小鼠模型中的治疗潜力。
方法：我们采用卵清蛋白（OVA）诱导的哮喘模型来评估FDE对气道嗜酸性粒细胞增多、气道高反应性（AHR）、黏液产生及IgE水平的影响。机制研究评估了调节性T细胞（Tregs）、树突状细胞表型、上皮屏障完整性及细胞因子信号传导。在哮喘患者的外周血单个核细胞（PBMCs）中进行了补充实验。
结果：FDE显著减轻了气道炎症和AHR，二级预防效果与全身地塞米松相当。FDE增强了Treg频率和CTLA-4表达，调节树突状细胞的MHC-II和PD-L1表达，并促进了免疫调节环境。它还恢复了上皮屏障完整性并增加了IL-33的释放，从而支持Treg的激活。在哮喘患者的PBMCs中，FDE增加了Treg，减少了Th2细胞，并抑制了CIITA，表明了类似的免疫调节作用。IL-33、双调蛋白（AREG）和Treg之间的相互作用揭示了一个强化免疫－上皮稳态的机制。
结论：在致敏后及过敏原激发期间施用FDE，能够减轻小鼠的关键哮喘特征，并在人类细胞中显示出转化潜力，这支持了将其作为一种新型的、源于环境的免疫调节策略进行开发。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（Allergy 2025 Oct 22;(0) DOI:10.1111/all.70121 IF: 8.706）
The Therapeutic Potential of Farm Dust Extracts in a Mouse Model of Eosinophilic Inflammation.
Rabia Ülkü, Korkmaz; Jimmy,
BACKGROUND: Asthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach.
METHODS: We used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors.
RESULTS: FDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis.
CONCLUSION: FDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy.
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