ArticleThe Journal of allergy and clinical immunology2026
Context-dependent regulation of mast cell-mediated food allergy in C57BL/6J mice.
Article in The Journal of allergy and clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIgE-mediated mast cell activation drives food-induced anaphylaxis in mouse models of food allergy (FA), but C57BL/6J mice are relatively resistant, whether to allergic diarrhea or systemic oral anaphylaxis. It is unclear whether this reflects a defect in mast cell activation, because these mice can produce allergen-specific IgE and respond to nonenteral allergens.
objectiveWe sought to determine whether tape-stripping-induced dermal injury could promote FA in systemically sensitized C57BL/6J mice and define the contributions of mucosal mast cells (MMCs) and connective tissue mast cells (CTMCs).
methodsC57BL/6J mice, wild-type littermates, and Mcpt5-Cre/DTA mice were subjected to systemic sensitization alone or combined tape-stripping/systemic sensitization. Anaphylaxis, mast cell hyperplasia, and mediator release were measured following oral allergen challenge.
resultsSystemically sensitized mice showed no impairment in IgE responses or MMC activation. However, food-induced intestinal and lethal oral anaphylaxis were observed only in tape-stripped mice. Dermal injury drove heterogeneous mast cell hyperplasia in multiple tissues, along with increased CD4 T cell- and innate lymphoid cell 2-derived IL-4 and intestinal cysteinyl leukotriene (CysLT) pathway genes. MMC and CTMC contributions were dose-dependent: repeated low-dose challenges favored leukotriene-dependent MMC responses, whereas a single high-dose challenge triggered CTMC-dependent systemic anaphylaxis. IL-4 further amplified CysLT gene expression and MMC hyperplasia, leading to CTMC-independent hypothermia. Arachidonate 5-lipoxygenase blockade reduced MMC-associated intestinal and oral anaphylaxis but did not affect CTMC-dependent systemic anaphylaxis.
conclusionsOverall, dermal injury combined with systemic sensitization promotes context-dependent FA in C57BL/6J mice through distinct mast cell subsets, with IL-4 and CysLTs shaping disease severity and phenotype.
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