IL-2-Agonist-Induced IFN-γ Exacerbates Systemic Anaphylaxis in Food Allergen-Sensitized Mice

• Published in: Frontiers in immunology Vol. 11; p. 596772
• Main Authors: Link, Christopher W M, Rau, Christina N, Udoye, Christopher C, Ragab, Mohab, Korkmaz, Rabia Ü, Comdühr, Sara, Clauder, Ann-Katrin, Lindemann, Timo, Frehse, Britta, Hofmann, Katharina, Almeida, Larissa N, Laumonnier, Yves, Beidaq, Asmaa El, Finkelman, Fred D, Manz, Rudolf A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 11.12.2020
• Subjects: Allergens - immunology; anaphylaxis; Anaphylaxis - etiology; Anaphylaxis - metabolism; Animals; Chickens; Cytokines - metabolism; Disease Models, Animal; Egg White - adverse effects; Female; Food - adverse effects; food allergy; Food Hypersensitivity - immunology; IFN-γ; IL-2; Immunization; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunology; Interferon-gamma - metabolism; Interleukin-2 - agonists; Mice; murine model; IFN-γ; IL-2; anaphylaxis; murine model; food allergy
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.596772

Food allergies are common, costly and potentially life-threatening disorders. They are driven by Th2, but inhibited by Th1 reactions. There is also evidence indicating that IL-2 agonist treatment inhibits allergic sensitization through expansion of regulatory T cells. Here, we tested the impact of an IL-2 agonist in a novel model for food allergy to hen´s egg in mice sensitized without artificial adjuvants. Prophylactic IL-2 agonist treatment expanded Treg populations and inhibited allergen-specific sensitization. However, IL-2 agonist treatment of already sensitized mice increased mast cell responses and allergic anaphylaxis upon allergen re-challenge. These effects depended on allergen-specific IgE and were mediated through IFN-γ, as shown by IgE transfer and blockade of IFN-γ with monoclonal antibodies. These results suggest that although shifting the allergic reaction toward a Treg/Th1 response inhibits allergic sensitization, the prototypic Th1 cytokine IFN-γ promotes mast cell activation and allergen-induced anaphylaxis in individuals that are already IgE-sensitized. Hence, while a Th1 response can prevent the development of food allergy, IFN-γ has the ability to exacerbate already established food allergy.