The airway as a route of sensitization to peanut: An update to the dual allergen exposure hypothesis

Abstract

Food allergies have increased at an alarming rate over the past 2 decades, indicating that environmental factors are driving disease progression. It has been postulated that sensitization to foods, in particular, peanut, occurs through impaired skin. Peanut allergens have been quantified in household dust and may be the culprit source. Indeed, T_H2 cell-skewing innate cytokines can be driven by application of food antigens on both intact and impaired skin of mice, resulting in antigen-specific IgE production and anaphylaxis following allergen exposure. However, allergy induction through the skin can be prevented by induction of oral tolerance before skin exposure. These observations led to the dual allergen exposure hypothesis, according to which oral exposure to food antigens leads to tolerance and antigen exposure on impaired skin leads to allergy. Here, we propose the airway as an alternative route of sensitization in the dual allergen exposure hypothesis that leads to food allergy. Specifically, we will provide evidence from mouse models and human cell-based studies that together implicate the airway as a plausible route of sensitization.

Keywords: Food allergy; airway; cutaneous; dual allergen exposure hypothesis; peanut allergy.

Figure 1.

An update to the dual allergen exposure hypothesis with the airway as a potential route of exposure. After exposure through the airway with an adjuvant or through skin with atopic dermatitis, in the context of increased innate cytokine production, peanut is taken up by dendritic cells, which migrate and present to naïve CD4⁺ T cells in the draining lymph nodes. These T cells become activated, produce Th2 cytokines and signal to B cells to produce peanut-specific IgE. In contrast, after oral exposure, peanut is taken up by dendritic cells in the tolerogenic environment of the GI tract, which migrate and present to naïve CD4⁺ T cells in the mesenteric lymph nodes. These T cells become programed into Tregs, leading to tolerance. Created with BioRender.com.