Cholera toxin induces food allergy through Th2 cell differentiation which is unaffected by Jagged2

• Published in: Life sciences (1973) 2020-12, Vol.263, p.118514, Article 118514
• Main Authors: Sun, Shanfeng, Jiang, Songsong, Wang, Junjuan, Chen, Cheng, Han, Shiwen, Che, Huilian
• Format: Article
• Language: English
• Subjects: Adjuvant; Adjuvants, Immunologic - toxicity; Allergens; Allergic reactions; Allergies; Animals; Bone marrow; CD4 antigen; Cell Differentiation; Cholera; Cholera toxin; Cholera Toxin - toxicity; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Differentiation (biology); Disease Models, Animal; Female; Food; Food allergies; Food allergy; Food Hypersensitivity - etiology; Food Hypersensitivity - metabolism; Food Hypersensitivity - pathology; Helper cells; Immune response; Immune system; Immunoregulation; Infections; Jagged-2 Protein - genetics; Jagged-2 Protein - metabolism; Ligands; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred BALB C; Mode of action; Notch signaling; Ovalbumin; Poisons; Receptors, Notch - metabolism; Signal transduction; Signaling; Th2 cell differentiation; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - metabolism; Toxins; Vibrio cholerae; Waterborne diseases
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118514

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 CD4+T 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. •The molecular basis and signaling mechanisms of cholera toxin during food allergy were investigated in this study.•We found cholera toxin induces expression of Jagged2, but Jagged2 is not required to promote Th2 cell differentiation.•This study provides scientific basis for understanding and studying the mechanism of food allergy.