Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization

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Abstract
Background Food allergies are an important cause of life‐threatening hypersensitivity reactions. Oral tolerance can be considered the default immune response to dietary antigens, with immune deviation resulting in allergic sensitization. However, primary sensitization to food allergens may not solely be through the gastrointestinal mucosa, as strong T‐helper type 2 (Th2)‐biased immunity can result from exposure to protein allergens on barrier‐disrupted skin. Objective The purpose of this study was to examine whether exposure to allergens through the skin may interfere with the normal development of oral tolerance and promote allergic sensitization to food proteins. Methods Female BALB/c mice were exposed epicutaneously to peanut protein and induction of systemic oral tolerance through high dose feeds of peanut protein was subsequently assessed. Other mice were rendered tolerant prior to epicutaneous peanut exposure. Sensitivity to peanut was determined by assessing delayed‐type hypersensitivity, proliferative, cytokine and antibody responses. Results Epicutaneous exposure to peanut protein induced potent Th2‐type immunity with high levels of IL‐4 and serum IgE. Primary skin exposure prevented the subsequent induction of oral tolerance to peanut in an antigen‐specific manner. Upon oral challenge, mice became further sensitized and developed strong peanut‐specific IL‐4 and IgE responses. Furthermore, animals with existing tolerance to peanut were partly sensitized following epicutaneous exposure. Conclusion Epicutaneous exposure to peanut protein can prevent induction of oral tolerance, and may even modify existing tolerance to peanut. Epidermal exposure to protein allergens selectively drives Th2‐type responses, and as such may promote sensitization to food proteins upon gastrointestinal exposure.