芽孢乳酸菌调控Foxp3+ Treg及其信号通路缓解对虾原肌球蛋白致敏反应的机制

Seafood allergy is among one of the most common food allergies, with fish and shellfish being two of the “big eight” categories of food allergens published by FAO, which can create both public health and economic concerns. Of which, tropomyosin was found to be a major agent for food hypersensitivity in crustaceans such as shrimp and crab. A great deal of scientific research has shown the cellular and humoral immune responses stimulated by probiotics for the beneficial effects on allergic disease. However, the mechanism by which they modulate the immune system is poorly understood. Previous studies demonstrated that oral treatment of tropomyosin-sensitized mice with Bacillus coagulans BC09.712 could significantly attenuate hypersensitivity responses and inhibit IgE production. In the present work, we will seek to identify if this strain could confer potent anti-allergic effects by a fine balance between allergen-specific CD4+Foxp3+regulatory T cells (Tregs) and T helper immune response as well as regulation by signaling pathways using shrimp tropomyosin as a model seafood allergen. The potential mechanisms include i) suppression of the capacity of dendritic cells to prime effector cells, ii) regulation of the Foxp3+ Tregs and other T helper cells balance, iii) manipulation of Treg-related signaling pathways, and iv) suppressing the production of allergen-specific IgE and mast cells degranulation by Tregs. This study will contribute to providing important evidence for prevention and control of seafood allergy.

水产品过敏在联合国粮农组织公布的八大食物过敏中占25%，已成为公众广泛关注的食品安全热点问题之一。原肌球蛋白是虾、蟹等甲壳类主要过敏原，研究发现包括芽孢乳酸菌等在内的益生菌能通过作用于Foxp3+Treg细胞等免疫系统显著缓解此类过敏，但相关机制尚不明确、说法不一。鉴于此，本项目着眼于Foxp3+Treg免疫平衡及其信号通路调控，以对虾原肌球蛋白作为过敏原，通过研究益生菌芽孢乳酸菌（BC09.712）诱导Foxp3+Treg负反馈调控致敏状态下肠道树突状细胞的激活效应；调控Foxp3+Treg与其它细胞亚群分化平衡；对Foxp3+Treg相关信号通路的调控；诱导Foxp3+Treg以平衡体内过敏效应等四个方面，深入探究芽孢乳酸菌免疫调控及缓解致敏反应的分子机制。本项目旨在充实和完善水产食品原料学中过敏原及免疫调控的相关基础理论，为水产食品过敏的预防与控制提供必要的依据和支撑。

水产品过敏在联合国粮农组织公布的八大食物过敏中占25%，已成为公众广泛关注的食品安全热点问题之一。原肌球蛋白是虾、蟹等甲壳类主要过敏原，研究发现包括芽孢乳酸菌等在内的益生菌能通过作用于Foxp3+Treg细胞等免疫系统显著缓解此类过敏，但相关机制尚不明确、说法不一。鉴于此，本项目着眼于Foxp3+Treg免疫平衡及其信号通路调控，以对虾原肌球蛋白作为过敏原，通过研究益生菌芽孢乳酸菌（BC09.712）诱导Foxp3+Treg负反馈调控致敏状态下肠道树突状细胞的激活效应；调控Foxp3+Treg与其它细胞亚群分化平衡；对Foxp3+Treg相关信号通路的调控；诱导Foxp3+Treg以平衡体内过敏效应等四个方面，深入探究芽孢乳酸菌免疫调控及缓解致敏反应的分子机制。本项目研究发现，树突状细胞介导了芽孢乳酸菌对T细胞分化的调控作用，揭示了Th1/Th2/Treg/Th17亚群细胞的分化和活性变化。进一步地，发现芽孢乳酸菌通过调控肠道菌群及其代谢产物发挥免疫调节功能的机制，揭示了关键的靶标微生物和代谢产物。本项目阐明了芽孢乳酸菌通过Treg细胞缓解食物过敏的具体机制，为进一步的食物过敏机制研究提供了理论依据，为肠道菌群调控食物过敏研究提供了靶点；本项目发现参与食物过敏过程的关键信号通路，为食物过敏的防治提供了潜在的靶点；研究结果揭示的关键肠道菌株和代谢产物为食物过敏患者的无损检测提供了生物标志物，而针对芽孢乳酸菌的详细分析为开发基于这一菌株的功能性食品和过敏人群特殊膳食提供了理论依据。综上所述，本项目充实和完善了水产食品原料学中过敏原及免疫调控的相关基础理论，为水产食品过敏的预防与控制提供必要的依据和支撑。