Food allergies are the result of a loss of tolerance to food and the development of Th2 cytokine-mediated inflammation. These conditions are a growing public health concern with an estimated 6% of children younger than three years old suffering from food allergies. Despite their increasing prevalence, the molecular and cellular immunological events that orchestrate the development and progression of food allergies remain poorly defined. One candidate for a factor that plays a critical role in the development of allergic food allergies is the cytokine TSLP (thymic stromal lymphopoietin). A variety of studies in both humans and mice implicate the TSLP in atopic disease processes, with elevated levels seen in the lungs of asthmatics and in the skin of individuals with atopic dermatitis. In addition, we have shown that mice lacking the TSLP receptor due to a targeted mutation are incapable of mounting a contact hypersensitive response to Th2-inducing haptens, and fail to develop antigen-driven airway inflammation. The studies in this application are designed to determine the role of TSLP in the development of allergic food allergy. An analysis of the role of TSLP in this disease will provide important information on the initiation and progression of the inflammatory response, and help to identify potential therapeutic targets for eventual treatment. Allergic food allergy is a common inflammatory disease of the gastrointestinal tract that affects up to 6% of children. In spite of this, the etiology and pathogenesis of allergic food allergy remains poorly understood The proposed experiments will help define the role of a novel cytokine, TSLP, in the induction and progression of allergic food allergy. This in turn will help guide efforts to develop new interventions for this and other inflammatory diseases that directly or indirectly target TSLP.
