Abstract
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.
Highlights
The Th2 cytokine IL-4 promotes class switching to IgE antibodies, which bind to the high affinity IgE receptor FceRI on mast cells [1,2,3]
Two putative allergens have been found in egg yolk (EY), chicken serum albumin a-livetin and yolk glycoprotein 42 [12, 13]. a-livetin has been identified as the major inhalant allergen in bird-toegg syndrome [14, 15], which links respiratory hypersensitivity to bird antigens to egg allergy [16]
Upon subsequent oral challenge with the same allergens, the sensitized mice developed diarrhea and anaphylaxis, which manifests as hypothermia. Using this model we found that IL-2/JES6 induces an IFN-g response; while this response inhibits Th2 cytokine and IgE production during the sensitization phase, it reduces the threshold for IgE-mediated mast cell activation in already sensitized mice
Summary
The Th2 cytokine IL-4 promotes class switching to IgE antibodies, which bind to the high affinity IgE receptor FceRI on mast cells [1,2,3]. Crosslinking of FceRI-bound IgE by antigen/allergen can induce type-1 hypersensitivity reactions, including those responsible for food allergies [4, 5]. Th1 reactions and their prototypic cytokine IFN-g can counterbalance Th2 responses, which reduces the production of IL-4 and IgE and thereby inhibits allergic sensitization [6, 7]. These observations suggested that restoring the Th1/Th2 balance by increasing Th1 responses could inhibit IgEmediated allergy [8]. Inhalation of avian airborne allergens first leads to respiratory hypersensitivity, subsequent ingestion of cross-reacting serum albumin in egg yolk can provoke gastro-intestinal symptoms, including diarrhea and vomiting
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