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. 2025 Aug 7;389(6760):eadp0240.
doi: 10.1126/science.adp0240. Epub 2025 Aug 7.

Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice

Laura R Hoyt  1   2 , Elise Liu  1   2   3 , Eli C Olson  4   5 , Danielle R Jacobsen  4   5 , Emily R Siniscalco  2   5 , Rebecca A Krier-Burris  4   5 , Kara G Greenfield  4   5 , Caleb D McBride  4   5 , Mia M Alfajaro  1   2 , Julien A R Amat  1   2 , Zhe Zhao  1   2 , Lan Xu  1   2 , Vivek Philip  6 , Aditi Verma  4   5 , Slim Fourati  4   5 , Donna L Senger  7   8 , Lingdi Zhang  9 , Supinda Bunyavanich  9 , Sarah E Glass  10   11   12 , Robert J Coffey  10   11   12 , Craig B Wilen  1   2 , Adam Williams  4   5 , Stephanie C Eisenbarth  1   2   4   5
Affiliations

Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice

Laura R Hoyt et al. Science. .

Abstract

Food-specific immunoglobulin E (IgE) triggers life-threatening anaphylaxis; however, for unclear reasons, some people with food-specific IgE are asymptomatic upon allergen consumption. We studied strains of mice with different sensitivities to anaphylaxis when orally challenged with allergen to identify possible causes. In resistant C57BL/6 mice, intestinal goblet cells transported less food allergen than did anaphylaxis-susceptible strains, even before allergic sensitization. In a forward genetic screen, resistance was correlated with dipeptidase 1 (Dpep1) variants. DPEP1 is expressed in intestinal epithelium and catabolizes leukotriene D4 (LTD4). Blocking DPEP1 with cilastatin, deleting Dpep1, or administering LTD4 orally enhanced allergen transport in resistant mice. Conversely, pretreatment of susceptible mice with a synthesis inhibitor, zileuton, abrogated allergen absorption and oral anaphylaxis, indicating that this could be an approach to treating food allergy.

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Conflict of interest statement

Competing interests: The authors declare that they have no competing interests.

The authors declare no competing financial interests.

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References

    1. Renz H et al. , Food allergy. Nat Rev Dis Primers 4, 17098 (2018). - PubMed
    1. Bartnikas LM, Sicherer SH, Fatal Anaphylaxis: Searching for Lessons from Tragedy. J Allergy Clin Immunol Pract 8, 334–335 (2020). - PMC - PubMed
    1. Alvaro M et al. , Tolerance to egg proteins in egg-sensitized infants without previous consumption. Allergy 69, 1350–1356 (2014). - PubMed
    1. Nicolaou N et al. , Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics. The Journal of allergy and clinical immunology 125, 191–197 e191–113 (2010). - PubMed
    1. Sampson HA, Ho DG, Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. The Journal of allergy and clinical immunology 100, 444–451 (1997). - PubMed

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