IL-2-Agonist-Induced IFN-γ Exacerbates Systemic Anaphylaxis in Food Allergen-Sensitized
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.
Link et al. 2020 Front. Immunol.
IFN-γ blockade normalizes IL-2 agonist-mediated exacerbation of anaphylaxis in allergic mice. Egg-allergic mice were treated daily on three consecutive days with IL-2/JES6 and challenged with allergen after the last IL-2/JES6 injection. Some groups additionally received one or three injections of anti-IFN-γ blocking antibodies, with all or only the last injection of IL-2/JES6, respectively. Mice were challenged 4 h after the last IL-2/JES6 injection. (A) Temperature drop curve. Representative data from one of two experiments are shown (B) Changes of maximal temperature drops before and after anti-IFN-γ blockade in individual mice (left, statistics: two way ANOVA with Sidak’s multiple comparison test) and maximal temperature drops after treatment in the various groups (right, statistics: Kruskal-Wallis Test with Dunn’s multiple comparison test) are shown, as indicated. Data are pooled from two independent experiments. Representative data from one of two experiments are shown (statistics: Kuskal-Wallis Test with Dunn’s multiple comparison test). *p < 0.05, **p < 0.005, ***p < 0.001, ****p < 0.0001.