Food allergies are a major cause of life-threatening hypersensitivity. Oral tolerance can be considered the default immune response to food antigens and disruption of this process may result in allergic sensitization. However, primary sensitization to food allergens may not be solely through the gastrointestinal mucosa, as strong Th2-biased immunity can be induced through cutaneous exposure to allergens. The purpose of this study was to determine whether exposure to allergens through the skin may interfere with oral tolerance and promote food allergies.

BALB/c mice were epicutaneously sensitized with peanut extract and induction of oral tolerance through single high dose feeds of peanut was subsequently assessed. Other mice were rendered tolerant prior to epicutaneous peanut exposure. Immune responses to peanut were determined by investigating DTH-, proliferative-, cytokine- and antibody responses.

Epicutaneous exposure to peanut induced potent Th2-type immunity with high levels of IL-4 and IgE. Primary skin exposure prevented induction of oral tolerance to peanut. Upon oral challenge mice were further sensitized and developed strong peanut-specific IL-4 and IgE responses (p<0.001) as well as clinical signs of anaphylaxis. Furthermore, animals with existing tolerance to peanut were partly sensitized following epicutaneous peanut exposure.

Epicutaneous sensitization and oral challenge may be used as a physiologically relevant model for food-induced sensitisation without the need for adjuvants. Epicutaneous exposure to peanut allergens prevents induction of oral tolerance and even partially abrogates existing tolerance to peanut. This implies that skin exposure to allergens specifically drives Th2 responses and may as such promote food allergy upon gastrointestinal exposure.