Analysis for acquiring and overriding oral tolerance in food allergy to use murine models

Abstract

Oral tolerance is an immune regulatory system for foods. Eating foods gives healthy people nutrition. However, foods are immune exclusion material in patients of food allergy. We thought possibilities for immune intolerance for foods, failing acquisition of oral tolerance and breaking acquired tolerance. Then, we made murine models for the possibilities. First, we made the food allergy model and oral tolerance model for ovalbumin (OVA). Experimental oral tolerance was induced by previously oral treatment with OVA solution before the sensitization by intraperitoneal injection of OVA. In the oral tolerance model, elevation of OVA-specific IgE was suppressed completely and anaphylaxis was not induced. Next, as the model of failing acquisition of oral tolerance, we used the food additives into the OVA solution for tolerance. As results, intake of the OVA solution with food additives prevented acquiring oral tolerance and induced anaphylaxis for OVA. Recently, “dual-allergen exposure hypothesis” was suggested. The hypothesis proposed allergic sensitization to food could occur through cutaneous sensitization and that consumption of food protein induced oral tolerance. We attempted to override oral tolerance for the food by sensitization via skin. We found that epicutaneous sensitization and sensitization by intradermal injection of OVA could override acquired oral tolerance. As two common denominators for immune intolerance for foods, we confirmed the change of migration of dendritic cells and prevention of inducing regulatory T cells.