Development of a Novel Treatment for Food Allergy Using a New Genetically Defined Mouse Model of the Disease

Abstract

Abstract : Loeys Dietz Syndrome (LDS) is an autosomal dominant disorder caused by mutations in the receptor for TGFbeta, a multifunctional cytokine that plays a key role in the development of mucosal tolerance. LDS patients exhibit an increased propensity to develop nearly all forms of allergic disease. The goals of this proposal are to examine whether LDS mice are more susceptible to developing peanut allergy, and whether treatment with losartan, an angiotensin II (ATII) receptor blocker that inhibits TGFbeta signaling, reduces the development and/or severity of allergic disease in this mouse model. Our experiments thus far suggest that LDS mice do exhibit more severe symptoms of anaphylaxis, using both a passive systemic anaphylaxis model as well as a murine model of peanut allergy. These data support a role for dysregulated TGFbeta signaling in the development of food-induced anaphylaxis, suggesting that targeting this pathway with pharmacologic agents may have therapeutic benefit. Over the next year, experiments will be focused on determining whether LDS mutations lead to increased susceptibility to food allergen sensitization, increased effector responses, or both. We will also examine how treatment with losartan modifies the allergic phenotype in LDS mice.