工程菌EcN预防小鼠过敏性哮喘症状研究
作者:
作者单位:

海南大学 生命健康学院,海南 海口

作者简介:

朱颖邦:完成实验,实验数据分析;裴业春:构思实验方法;麦艳琪:实验图表处理;柳贤德:实验思路设计。

基金项目:

国家自然科学基金(32260854)


Prevention of allergic asthma symptoms in mice by an engineered bacterial strain EcN
Author:
Affiliation:

School of Life and Health Sciences, Hainan University, Haikou, Hainan, China

Fund Project:

This work was supported by the National Natural Science Foundation of China (32260854).

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    摘要:

    过敏性哮喘是一种常见的慢性炎症性疾病,其特征为气道高反应性和呼吸道炎症,常由吸入性过敏原(如宠物皮屑、花粉等)触发。近年来,研究发现辅助性T细胞(Th细胞)在过敏性哮喘的免疫调节中扮演着关键角色,特别是Th2型细胞通过分泌IL-4、IL-5等细胞因子促进嗜酸性粒细胞和肥大细胞的增殖,从而加剧气道炎症。此外,Th17型细胞的活化也与过敏性哮喘的炎症反应密切相关。因此,调节Th1/Th2和Th17/Treg细胞平衡是治疗过敏性哮喘的有效策略。目的 探讨过敏性哮喘的发病机制及新型治疗方法。方法 构建一种特异性表达狗过敏原Canf-1的工程菌EcNcanf-1,通过pBAD启动子在小鼠肺部可控表达Canf-1。结果 EcNcanf-1可调节肺部细胞因子的表达,特别是降低IL-6、IL-5和IL-13的水平,同时上调IFN-γ、TGF-β和IL-10等细胞因子,从而缓解肺部过敏性症状。EcNcanf-1还可下调Th2和Th17细胞在过敏症状下的异常表达,增强Th1和Treg细胞的功能。EcNcanf-1还可减少肺部肥大细胞的数量,降低血管通透性,减轻过敏原引起的体温下降和气道狭窄症状。研究表明,EcNcanf-1在调节免疫反应和缓解过敏性肺部炎症方面具有重要作用。结论 EcNcanf-1通过调节免疫细胞和细胞因子的表达,为过敏性哮喘提供了一种新的治疗途径。这不仅为理解过敏性哮喘的免疫机制提供了新的见解,也为开发新的生物靶向治疗策略提供了科学依据。

    Abstract:

    Allergic asthma is a prevalent chronic inflammatory disease characterized by airway hyperresponsiveness and airway inflammation, often triggered by inhalant allergens such as pet dander and pollen.Objective Studies have revealed that helper T cells (Th cells) play a crucial role in the immune regulation of allergic asthma. Particularly, Th2 cells exacerbate airway inflammation by secreting cytokines such as interleukin (IL)-4 and IL-5, which promote the proliferation of eosinophils and mast cells. Additionally, the activation of Th17 cells is closely related to the inflammatory response in allergic asthma. Therefore, modulating the balance of Th1/Th2 and Th17/Treg cells has become an effective strategy for treating allergic asthma. This study explores the pathogenesis of allergic asthma and novel therapeutic approaches.Methods We constructed an engineered bacterium EcNcanf-1 specifically expressing the dog allergen Canf-1. Using the pBAD promoter, we controlled the expression of Canf-1 in the lungs of mice.Results EcNcanf-1 exerted immunomodulatory effects by regulating pulmonary cytokine expression profiles, specifically downregulating the expression of pro-inflammatory cytokines including IL-6, IL-5, and IL-13, while upregulating the expression of anti-inflammatory mediators such as interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), and IL-10, thus alleviating allergic symptoms in the lungs. EcNcanf-1 demonstrated remarkable efficacy in suppressing the pathological overexpression of Th2 and Th17 lymphocyte subsets under allergic conditions, while enhancing the functions of Th1 and regulatory T cells. Furthermore, EcNcanf-1 significantly reduced pulmonary mast cell infiltration, attenuated vascular permeability, and mitigated allergen-induced hypothermia and airway constriction. These findings demonstrated that EcNcanf-1 played a pivotal role in immune homeostasis regulation and represented a promising therapeutic candidate for allergic pulmonary inflammation through its multifaceted modulation of immunological pathways.Conclusion EcNcanf-1 provides a new therapeutic avenue for allergic asthma by modulating the expression of immune cells and cytokines. This not only offers new insights into the immune mechanisms of allergic asthma but also provides a scientific basis for the development of new targeted biological treatment strategies.

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朱颖邦,裴业春,麦艳琪,柳贤德. 工程菌EcN预防小鼠过敏性哮喘症状研究[J]. 微生物学报, 2025, 65(7): 2903-2919

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  • 收稿日期:2024-11-29
  • 在线发布日期: 2025-07-04
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