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首页> 外文期刊>Allergology international: official journal of the Japanese Society of Allergology >Beneficial effects of Galectin-9 on allergen-specific sublingual immunotherapy in a Dermatophagoides farinae-induced mouse model?of chronic asthma
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Beneficial effects of Galectin-9 on allergen-specific sublingual immunotherapy in a Dermatophagoides farinae-induced mouse model?of chronic asthma

机译:Galectin-9对 Dermatophagoides farinae 诱发的慢性哮喘小鼠模型的变应原特异性舌下免疫治疗的有益作用

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Background Allergen-specific sublingual immunotherapy is a potential disease-modifying treatment for allergic asthma. Galectin-9 (Gal-9), a β-galactoside-binding protein with various biologic effects, acts as an immunomodulator in excessive immunologic reactions by expanding regulatory T cells (Treg) and enhancing transforming growth factor (TGF)-β signaling. We investigated the efficacy of sublingually administered Gal-9 as an adjuvant to a specific allergen in a Dermatophagoides farinae (Df)-induced mouse model of chronic asthma. Methods BALB/c mice were intranasally sensitized with Df extract 5 days/week for 5 weeks, and then sublingual Df-allergen extract for 2 weeks (5 days/week). Three days after the final sublingual treatment, mice were intranasally challenged with Df extract. The early asthmatic response (EAR) was evaluated 5?min after the last Df challenge. Airway hyperresponsiveness (AHR) was assayed and bronchoalveolar lavage (BAL) was performed 24?h after the last allergen challenge. Serum IgE and cytokine levels, and number of inflammatory cells in the BAL fluid (BALF) were analyzed. Results Sublingual Df treatment in the presence of Gal-9, but not alone, significantly reduced AHR; EAR; number of eosinophils and interleukin-13 in the BALF; and serum IgE levels. BALF TGF-β1 levels were significantly increased in the presence of Gal-9 compared with Df alone. Treg depletion blocked the inhibitory effects of Gal-9 on the EAR, AHR, eosinophilic airway inflammation, and Df-specific serum IgE levels, and suppressed BALF TGF-β1 levels. Conclusions Gal-9 exhibited beneficial effects of sublingual Df allergen-specific immunotherapy in a Df-induced mouse model of chronic asthma, possibly by Gal-9-induced TGF-β1 production in the lung.
机译:背景技术过敏原特异性舌下免疫疗法是一种可能的变应性哮喘治疗方法。 Galectin-9(Gal-9)是一种具有多种生物学效应的β-半乳糖苷结合蛋白,通过扩展调节性T细胞(Treg)和增强转化生长因子(TGF)-β信号传导,在过度的免疫反应中充当免疫调节剂。我们调查了舌下给予Gal-9作为特定过敏原佐剂的功效,该过敏原是由Dermatophagoides farinae(Df)诱导的慢性哮喘小鼠模型中的特定变应原。方法用Df提取物对BALB / c小鼠鼻内增敏5天/周,持续5周,然后舌下Df-过敏原提取物增敏2周(5天/周)。最后的舌下治疗三天后,用Df提取物对小鼠进行鼻内攻击。最后一次Df攻击后5分钟评估早期哮喘反应(EAR)。在最后一次过敏原攻击后24小时,对气道高反应性(AHR)进行测定,并进行支气管肺泡灌洗(BAL)。分析了血清IgE和细胞因子水平,以及BAL液(BALF)中炎性细胞的数量。结果在存在Gal-9的情况下(但不是单独存在)舌下Df治疗可显着降低AHR;耳; BALF中嗜酸性粒细胞和白介素13的数量;和血清IgE水平。与单独的Df相比,在Gal-9存在下,BALFTGF-β1水平显着增加。 Treg耗竭可阻断Gal-9对EAR,AHR,嗜酸性气道炎症和Df特异性血清IgE水平的抑制作用,并抑制BALFTGF-β1水平。结论Gal-9在Df诱导的慢性哮喘小鼠模型中具有舌下Df过敏原特异性免疫疗法的有益作用,可能是Gal-9诱导的肺TGF-β1产生的结果。

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