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局部鼻内免疫疗法:粉尘螨-壳聚糖疫苗对小鼠哮喘的疗效

Local nasal immunotherapy: efficacy of Dermatophagoides farinae-chitosan vaccine in murine asthma.

作者信息

Liu Zhigang, Guo Hua, Wu Yiaojiong, Yu Haiqiong, Yang Haitao, Li Jing

机构信息

Allergy and Immunology Institute, School of Medicine, Shenzhen University, Shenzhen, PR China.

出版信息

Int Arch Allergy Immunol. 2009;150(3):221-8. doi: 10.1159/000222674. Epub 2009 Jun 3.

Abstract

BACKGROUND

Local nasal immunotherapy has been reported to be effective for airway allergic diseases. A biodegradable material, chitosan (CS), has been reported to be safe and effective in allergen delivery. In this study, we tested immunotherapeutic efficiency by intranasal administration of Der f entrapped in CS microparticles to sensitized mice.

METHODS

BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by intranasal treatment with PBS, CS, Der f or Der f-CS nano-vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week, and we analyzed their clinical symptoms, antibody expression levels, cytokine levels, T cell proliferation and regulatory T cell numbers.

RESULTS

Mice treated with intranasal Der f-CS nano-vaccine prior to challenge displayed an alleviated spectrum of symptoms including airway hyper-reactivity, lung inflammation and mucus production and had fewer eosinophilic cells in bronchoalveolar lavage fluid (BALF). Interestingly, the cytokine levels in Der f-specific IgE were reduced, but IgA in serum and BALF was increased. We also observed that IL-4 was reduced and IFN-gamma and IL-10 were increased among splenocytes and in BALF, which inhibits Der f-specific T-cell proliferation in splenocytes and increases regulatory T cells in the spleen. However, the mice challenged without intranasal Der f or Der f-CS vaccine treatment developed allergic asthma.

CONCLUSION

Our results illustrate that intranasal administration of Der f-CS nano-vaccine plays roles in immunologic protection in murine allergic asthma by inducing regulatory T cells and Th1-type reaction.

摘要

背景

局部鼻内免疫疗法已被报道对气道过敏性疾病有效。一种可生物降解的材料,壳聚糖(CS),已被报道在变应原递送中安全有效。在本研究中,我们通过向致敏小鼠鼻内给予包裹在CS微粒中的Der f来测试免疫治疗效果。

方法

用吸附于明矾的Der f提取物对BALB/c小鼠进行腹腔致敏,随后用PBS、CS、Der f或Der f-CS纳米疫苗进行鼻内治疗6周。随后,用Der f提取物对小鼠进行鼻内激发1周,我们分析了它们的临床症状、抗体表达水平、细胞因子水平、T细胞增殖和调节性T细胞数量。

结果

在激发前接受鼻内Der f-CS纳米疫苗治疗的小鼠表现出一系列症状减轻,包括气道高反应性、肺部炎症和黏液产生,支气管肺泡灌洗液(BALF)中的嗜酸性粒细胞较少。有趣的是,Der f特异性IgE中的细胞因子水平降低,但血清和BALF中的IgA增加。我们还观察到,脾细胞和BALF中的IL-4降低,IFN-γ和IL-10增加,这抑制了脾细胞中Der f特异性T细胞的增殖,并增加了脾脏中的调节性T细胞。然而,未接受鼻内Der f或Der f-CS疫苗治疗而被激发的小鼠发生了过敏性哮喘。

结论

我们的结果表明,鼻内给予Der f-CS纳米疫苗通过诱导调节性T细胞和Th1型反应在小鼠过敏性哮喘的免疫保护中发挥作用。

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