Epicutaneously sensitized food-induced anaphylaxis is ameliorated with "oral tolerance" to antigen.

Food allergy is an antigen-specific immunological adverse reaction after exposure to a given food. Multiple clinical studies showed that oral immunotherapy (OIT) is effective for the prevention and treatment for food allergy that is developed in infants and children. However, the effectiveness of OIT for epicutaneously sensitized food allergy remains unclear. Previously, we established a mouse model of epicutaneous-sensitized food allergy. In this model, systemic allergic reaction including intestinal and skin symptoms, such as anaphylaxis, was observed. We treated this model with OIT in two ways (OIT before sensitization or OIT during the sensitization phase) and evaluated the preventive effect of both methods. OIT before sensitization significantly ameliorated mast cell degranulation in sensitized skin, but there was no decrease in rectal temperatures or in mast cell degranulation in the jejunum. However, OIT administered during the sensitization phase significantly ameliorated the decrease in rectal temperature and mast cell degranulation in the skin and jejunum. OIT before sensitization increased the regulatory T cells in mesenteric lymph node (MLN), but not in the spleen, and it reduced antigen-specific IgG, but not IgE, production compared with the non-OIT control. However, OIT during sensitization caused a greater increase in regulatory T cells in both the MLN and spleen and reduced antigen-specific IgE and IgG generation compared with the non-OIT control group. Thus, OIT during the sensitization phase was effective for the prevention of epicutaneous-sensitized food allergy.

Basophils and mast cells are crucial for reactions due to epicutaneous sensitization to ovalbumin.

The prevalence of food allergies worldwide has increased recently. Epicutaneous sensitization to antigen could be a method to study food allergy. To clarify the mechanisms of food allergy, we established a mouse model of epicutaneous sensitization using ovalbumin (OVA). BALB/c mice were sensitized by three-time application of OVA to tape-stripped skin (1-week sensitization at 2-week intervals) and oral challenge of OVA undertaken. Rectal temperature was monitored. Blood and tissue (skin and jejunum) of challenged mice were taken. Numbers of mast cells (MCs) and basophils were counted. Serum and/or tissue levels of OVA -specific IgE and IgG antibodies and several cytokines were measured using enzyme-linked immunoassay kits. MC and basophil depletion experiments were undertaken. In OVA/epicutaneous-sensitized and orally challenged mice, systemic anaphylaxis (as evidenced by reduced rectal temperature) was observed. Levels of OVA-specific IgE and IgG antibodies were increased in these mice, as were increased number of MCs and basophils. Serum levels of MC protease 1 were increased significantly. Basophil and MC depletion experiments revealed that they both participate in reactions. Increased production of thymic stromal lymphopoietin (TSLP) at skin sites of OVA sensitization was noted. We speculate that TSLP produced from epidermal cells during antigen sensitization can enable basophils to promote a T helper (Th)2 immune reaction, leading to and systemic anaphylaxis by antigen-specific IgE-bearing MCs. This TSLP-basophils-MC axis could be a novel therapeutic target against food allergy.