Recent developments in understanding the mechanisms of food allergy.

PURPOSE OF REVIEW: The prevalence of food allergy is rising globally. This review will discuss recent discoveries regarding the immunologic mechanisms that drive the initial sensitization and allergic response to food antigens, which may inform prevention and treatment strategies. RECENT FINDINGS: Tolerance to food antigens is antigen-specific and promoted by oral exposure early in life and maternal transfer of immune complexes via breast milk. IgG can inhibit both the initiation and effector phases of allergic responses to food antigens in mice, and high levels of food-specific IgG4 are associated with acquisition of tolerance in humans. Disruption of the skin barrier provides a route for food sensitization through the actions of mast cells, type 2 innate lymphoid cells, and IL-33 signaling. Regulatory T cells (Tregs) promote acquisition of oral tolerance, although defects in circulating allergen-specific Tregs are not evident in children with established food allergy. Certain microbes can offer protection against the development of IgE and food allergic responses, while dysbiosis increases susceptibility to food allergy. SUMMARY: Tolerance to food antigens is antigen-specific and is promoted by oral exposure early in life, maternal transfer of immune complexes, food-specific IgG, Tregs, an intact skin barrier, and a healthy microbiome.