Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
College of Food Science and Engineering, Yangzhou University, No.88 Daxue South Road, Hanjiang District, Yangzhou, Jiangsu Province, China.
Life Sci. 2020 Dec 15;263:118514. doi: 10.1016/j.lfs.2020.118514. Epub 2020 Oct 1.
Cholera toxin is often used to induce food allergies. However, its exact mode of action and effect remain ambiguous. In this study, we established a BALB/c mouse cholera toxin/ovalbumin-induced food allergy model to determine the molecular basis and signaling mechanisms of the immune regulation of cholera toxin during food allergy.
The adjuvant activity of cholera toxin was analyzed by establishing mouse allergy model, and the allergic reaction of each group of mice was evaluated. The effect of cholera toxin on Th1/Th2 cell differentiation was analyzed to further explore the role of cholera toxin in allergen immune response. We stimulated bone marrow-derived dendritic cells (BMDCs) with cholera toxin in vitro to investigate the effect of cholera toxin on Notch ligand expression. BMDCs and naive CD4T cells were co-cultured in vitro, and their cytokine levels were examined to investigate whether cholera toxin regulates Th cell differentiation via the Jagged2 Notch signaling pathway.
The results showed that in the presence of allergens, cholera toxin promotes Th2 cell differentiation and enhances the body's immune response. Cholera toxin induces expression of the Notch ligand Jagged2, but Jagged2 Notch signaling pathway is not required to promote BMDCs-mediated differentiation of Th2 cells.
This study initially revealed the mechanism by which cholera toxin plays an adjuvant role in food allergy, and provides reference for future related research.
霍乱毒素常用于诱导食物过敏。然而,其确切作用机制和效果仍不清楚。本研究建立了 BALB/c 小鼠霍乱毒素/卵清蛋白诱导的食物过敏模型,以确定霍乱毒素在食物过敏过程中免疫调节的分子基础和信号机制。
通过建立小鼠过敏模型分析霍乱毒素的佐剂活性,并评估各组小鼠的过敏反应。分析霍乱毒素对 Th1/Th2 细胞分化的影响,进一步探讨霍乱毒素在变应原免疫反应中的作用。我们用霍乱毒素体外刺激骨髓来源的树突状细胞(BMDCs),研究霍乱毒素对 Notch 配体表达的影响。体外共培养 BMDCs 和幼稚 CD4T 细胞,检测细胞因子水平,探讨霍乱毒素是否通过 Jagged2 Notch 信号通路调节 Th 细胞分化。
结果表明,在过敏原存在的情况下,霍乱毒素促进 Th2 细胞分化,增强机体免疫反应。霍乱毒素诱导 Notch 配体 Jagged2 的表达,但 Jagged2 Notch 信号通路不是促进 BMDCs 介导的 Th2 细胞分化所必需的。
本研究初步揭示了霍乱毒素在食物过敏中发挥佐剂作用的机制,为今后相关研究提供参考。