Food allergy: Insights into etiology, prevention, and treatment provided by murine models

Abstract

Food allergy is a rapidly growing public health concern because of its increasing prevalence and life-threatening potential. Animal models of food allergy have emerged as a tool for identifying mechanisms involved in the development of sensitization to normally harmless food allergens, as well as delineating the critical immune components of the effector phase of allergic reactions to food. However, the role animal models might play in understanding human diseases remains contentious. This review summarizes how animal models have provided insights into the etiology of human food allergy, experimental corroboration for epidemiologic findings that might facilitate prevention strategies, and validation for the utility of new therapies for food allergy. Improved understanding of food allergy from the study of animal models together with human studies is likely to contribute to the development of novel strategies to prevent and treat food allergy.

Keywords: AD; Atopic dermatitis; CM; CT; Cholera toxin; Cow's milk; DC; Dendritic cell; FAHF-2; Food Allergy Herbal Formula-2; Food allergy; Forkhead box protein 3; Foxp3; GF; Germ free; LP; Lamina propria; MLN; Mesenteric lymph node; OIT; Oral immunotherapy; PAF; Platelet-activating factor; Regulatory T; SEB; Staphylococcal enterotoxin B; Treg; anaphylaxis; microbiota; murine model; regulatory T cells.

Figure 1. Possible mechanisms of allergic sensitization to food antigens

Altered skin barrier (or adjuvant) allows antigen entry and stimulates keratinocyte to produce TSLP that activates skin derived DCs, which promote the differentiation of Th2 cells and IgE producing B cells in draining lymph node. Orally administered mucosal adjuvant induces IL-33 secretion by intraepithelial cells that upregulates OX40L expression on DCs that promote Th2 response in MLN. Increased Th2 cytokines and IgE mediate intestinal expansion of mast cells that may in turn recruit Th2 cells to the intestine and increase intestinal permeability that results in the development of gastrointestinal symptoms including diarrhea. Increased Th2 milieu, such as those in Il4raF709 mice, may hinder Treg cell function that leads to loss of oral tolerance to food antigens.