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

Nature Reviews Immunology volume 25, pages 783–797 (2025)Cite this article

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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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Fig. 1: Food tolerance.
Fig. 2: Food sensitization and allergic gut tropism.
Fig. 3: Mast cell effector functions in food allergy.

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Authors and Affiliations

  1. Division of Experimental Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI, USA

    Nicholas W. Lukacs & Simon P. Hogan

  2. Mary H Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA

    Nicholas W. Lukacs & Simon P. Hogan

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  1. Nicholas W. Lukacs
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  2. Simon P. Hogan
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The authors contributed equally to all aspects of the article.

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Correspondence to Simon P. Hogan.

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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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Glossary

Alarmins

Alarmins are endogenous damage-associated molecular patterns (DAMPs) released during cellular stress, trauma or necrosis that function as early immunological danger signals. Three key epithelial-derived alarmins — TSLP, IL-25 and IL-33 act primarily through innate lymphoid cells type 2 (ILC2s) and dendritic cells to orchestrate type 2 immune responses and contribute to the pathobiology and pathophysiology of allergic responses.

Atopic dermatitis

Also known as eczema, is the most common chronic skin disease of young children characterized by pruritic (itching) skin lesions. A chronic inflammatory response induces redness, swelling, itching and cracking of the skin layer, which causes weakening of the skin barrier and permits environmental and food allergen penetration.

Filaggrin

Filaggrin (filament-aggregating protein) is a key structural protein essential for terminal differentiation of the epidermis and formation of the skin barrier.

Oral tolerance

An active process of local and systemic immune unresponsiveness to orally delivered antigens, including food.

Petechiae

A skin condition that appears as small red, purple or brown spots resulting from capillary leakage.

TMEM79

A transmembrane protein that contributes to epidermal integrity and skin barrier function.

Tryptase

Alpha-tryptase is a mast cell-derived protease.

Wheal-and-flare reaction

The wheal-and-flare response is a type of immediate hypersensitivity reaction that can occur within minutes of an allergen being injected into the skin. It is characterized by the raising of the skin (swelling) at the injection site because of fluid leaking into the tissue (wheal). This followed by redness of the skin, resulting from the dilation of blood vessels (flare). A wheal-and-flare reaction is a result of immunoglobulin E-dependent basophils and mast cells activation.

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Lukacs, N.W., Hogan, S.P. Food allergy: begin at the skin, end at the mast cell?. Nat Rev Immunol 25, 783–797 (2025). https://doi.org/10.1038/s41577-025-01185-y

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