Tu103 - Cysteinyl Leukotrienes Promote Anaphylaxis to Ingested Allergens

Abstract Text: Food allergy affects approximately 8% of US children with increasing prevalence and limited therapeutic options. Although food-specific IgE is necessary for anaphylaxis in humans, it is not sufficient, indicating that other factors contribute to anaphylaxis susceptibility. We found that despite equivalent levels of food-specific IgE and anaphylactic response upon systemic challenge in both C57BL/6 and C3H/HeJ mouse strains, the C57BL/6 mouse strain is uniquely resistant to anaphylaxis following the ingestion of food allergens. By crossing C57BL/6 and C3H/HeJ mice and performing a genetic screen, we found that oral anaphylaxis resistance corresponded with allelic variants of Dipeptidase 1 (Dpep1). Dpep1 encodes the enzyme DPEP1, which catabolizes leukotriene D4 (LTD4). DPEP1 activity was significantly higher in intestinal tissue from C57BL/6 mice compared to C3H/HeJ mice despite equivalent protein levels. In addition, C57BL/6 mice had lower intestinal levels of LTD4. Genetic deletion of Dpep1 or treatment with exogenous LTD4 rendered C57BL/6 mice susceptible to oral anaphylaxis while blockade of leukotriene synthesis protected C3H/HeJ mice from to oral anaphylaxis. These data suggest that leukotrienes regulate susceptibility to oral anaphylaxis in mice. Ongoing research will determine whether altering the leukotriene pathway in humans can similarly prevent anaphylactic response to ingested allergens.