Food additives initiate breaking the oral tolerance in a murine food allergy model

[Speaker] Yuri Tanaka:1
[Co-author] Hirotaka Yamashita:1, Kenichi Saneyasu:1, Hiroyuki Tanaka:1, Naoki Inagaki:1
1:Laboratory of Pharmacology, Gifu Pharmaceutical University, Japan

The prevalence cases of food allergies have dramatically increased in the past few decades; however, the causes of this increase are not clearly known. Food allergies mostly develop in the early time of life. Oral intake of food proteins acquires oral tolerance for the food. The patients with food allergy fail to acquire the essential immune tolerance. We presumed developing food allergy was related to dietary environment at the stage of infancy. Our research projects have been focused on the intakes of food additives, such as sweeteners, preservatives, colorings and flavorings. In our previous study, murine models of food allergy and oral tolerance for food were reported. In the present study, we demonstrate the results of evaluation of food additives associating with failure of oral tolerance, and mechanism of breaking oral tolerance. In the present model, ovalbumin (OVA) as food antigen was used. Food allergy was induced by oral administration of OVA to mice sensitized by injection of OVA/alum. Experimental oral tolerance was induced by previous oral treatment with OVA. The elevation of OVA-specific IgE and development of food allergy, such as hypothermia and allergic diarrhea, were inhibited by inducing the tolerance. Next, we estimated the effect of saccharin sodium, acesulfame potassium, aspartame, benzoic acid, silicon dioxide, annatto pigment etc. on breaking oral tolerance. We detected OVA-specific IgE in blood to administer saccharin in the induction of oral tolerance. Then, saccharin treatment inhibited acquiring the tolerance and induced food allergy. We found increasing proportions of CD4+CD25+ regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) in the mice with oral tolerance was suppressed by the saccharin treatment. Furthermore, we analyzed migration of dendritic cells (DCs) into MLNs. It was known that CD103+DCs tend to activate or differentiate Tregs and CD11b+CD103-DCs associate allergic responses. Saccharin accelerated migration of the allergic CD11b+CD103-DCs and decelerated tolerogenic CD103+DCs into MLNs. Our data might suggest that intakes of food additives are one of the risk factor for onset of food allergy.
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