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Murine anaphylaxis to food requires cysteinyl leukotriene-mediated absorption of allergens in the gut.

GSE285568 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/08/13 Platform GPL34290
Summary
Food-specific IgE triggers life-threatening anaphylaxis; however, some people with food-specific IgE are asymptomatic upon allergen consumption. Using murine food allergy models, we discovered an unexpected pathway regulating the ability of food allergens to trigger anaphylaxis. C57BL/6 mice are uniquely resistant to anaphylaxis when challenged orally; we show that goblet cells transport less food allergens relative to anaphylaxis-susceptible strains, even prior to allergic sensitization. In a forward genetic screen, oral anaphylaxis resistance correlated with Dipeptidase1 (Dpep1) allelic variants. DPEP1 is expressed in intestinal epithelium and catabolizes leukotriene D4 (LTD4). Blocking DPEP1 with cilastatin, genetically deleting Dpep1, or oral administration of LTD4 enhanced allergen transport in resistant mice. Conversely, pre-treatment of susceptible mice with a leukotriene synthesis inhibitor, zileuton, abrogated allergen absorption from the gut and subsequent oral anaphylaxis. Inhibiting leukotrienes may be a novel treatment for food allergy.
Published in
Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice
Hoyt LR, Liu E, Olson EC et al. · Science (New York, N.Y.) 2025 · PMID 40773557 · doi:10.1126/science.adp0240
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Also filed as BioProject PRJNA1204804 and SRA study SRP554613. Searching any of these in the dataset finder brings you back here.

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