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Review
. 2025 Nov;25(11):783-797.
doi: 10.1038/s41577-025-01185-y. Epub 2025 Jun 26.

Food allergy: begin at the skin, end at the mast cell?

Affiliations
Review

Food allergy: begin at the skin, end at the mast cell?

Nicholas W Lukacs et al. Nat Rev Immunol. 2025 Nov.

Abstract

Food allergy is an acute IgE-mediated reaction that occurs in response to food components and affects 1-10% of the global population. It is often thought to be a disease of the gastrointestinal tract, in which oral exposure to a food allergen induces an IgE-sensitizing response that primes the host immune system to react to the eliciting allergen following subsequent oral exposure. However, emerging evidence from clinical and basic research studies suggests that maladaptive immune responses in the skin also contribute to the development of food allergy. These responses can promote the development of food-specific IgE and reshape the gut immune microenvironment in a manner that predisposes to IgE-mediated activation of mast cells and clinical manifestations of allergic disease following subsequent food exposures. In this Review, we discuss how different routes of exposure to food antigens can contribute to allergic sensitization and describe how mast cells ultimately drive the allergic reaction to these food allergens.

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Conflict of interest statement

Competing interests: N.W.L. is the Chief Scientific Officer for Opsidio, which is developing antibodies to stem cell factor to target mast cells. S.P.H. receives research funding from Regeneron Pharmaceuticals.

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