Deciphering the black box of food allergy mechanisms

Abstract

Objective: To review our current understanding of immunotherapy, the immune mechanisms underlying food allergy, and the methodological advances that are furthering our understanding of the role of immune cells and other molecules in mediating food allergies.

Data sources: Literature searches were performed using the following combination of terms: allergy, immunotherapy, food, and mechanisms. Data from randomized clinical studies using state-of-the-art mechanistic tools were prioritized.

Study selections: Articles were selected based on their relevance to food allergy.

Results: Current standard of care for food allergies is avoidance of allergenic foods and the use of epinephrine in case of severe reaction during unintentional ingestion. During the last few decades, great strides have been made in understanding the cellular and molecular mechanisms underlying food allergy, and this information is spearheading the development of exciting new treatments.

Conclusion: Immunotherapy protocols are effective in desensitizing individuals to specific allergens; however, recurrence of allergic sensitization is common after discontinuation of therapy. Interestingly, in a subset of individuals, immunotherapy is protective against allergens even after discontinuation of immunotherapy. Whether this protection is permanent is currently unknown because of inadequate long-term follow-up data. Research on understanding the underlying mechanisms may assist in modifying protocols to improve outcome and enable sustained unresponsiveness, rather than a temporary relief against food allergies. The cellular changes brought about by immunotherapy are still a black box, but major strides in our understanding are being made at an exciting pace.

Figure 1

Breakdown of the epidermal barrier increases secretion of epithelium-derived cytokines (interleukin [IL] 25, IL-33, and thymic stromal lymphopoietin [TSLP]), promoting increases in T_H2 cells, IgE class switching by B cells, and accumulation of proinflammatory mediators. DC indicates dendritic cell.

Figure 2

Tolerance is an active immune process. Dendritic cells (DCs) present food antigens to naive T cells, promoting their differentiation into T-regulatory cells (Tregs). These cells secrete interleukin 10 (IL-10) and transforming growth factor β (TGF-β), which suppresses allergic response. IDO indicates indoleamine 2,3-dioxygenease.

Figure 3

During immunotherapy, current evidence indicates increases in T-regulatory cells (Tregs) and IgG4 class switching by B cells. Mast cells and basophil activation is decreased. IgG4 may compete with IgE to dampen allergic response. IL-10 indicates interleukin 10; TGF-β, transforming growth factor β.