Impact/Purpose:

To test the role of TSLP in food allergy, its mechanism of action, and its regulation in the gastrointestinal tract.

Description:

Food allergy is a major public health problem affecting 6-8% of children in the United States, but there is a dearth of information on pathogenesis or preventative strategies. The proposed studies aim to assess mechanisms of food allergy pathogenesis and identify potential triggers of allergic sensitization. This information would be of value in the design of novel therapeutic approaches and development of public health strategies for the prevention of food allergy. Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that has a central role in the development of allergic inflammation in the skin and lung. In the gastrointestinal tract TSLP has a regulatory function, however we hypothesize that an over-expression of TSLP may promote allergic sensitization to food allergens.

Record Details:

Record Type:PROJECT( ABSTRACT )

Start Date:12/01/2008

Completion Date:11/30/2010

Record ID: 203663

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Related Organizations:

Role :OWNER

Organization Name :MOUNT SINAI SCHOOL OF MEDICINE

Mailing Address :1 Gustave L Levy Pl

Citation :New York

State :NY

Zip Code :10029

Project Information:

Approach :

We will use murine models of IgE-mediated food allergy to test the role of TSLP in the inductive and effector phases of food allergy. We will use TSLP R-/- mice to test the role of TSLP in oral sensitization to food allergens, allergen-induced anaphylaxis, and allergen-induced gastrointestinal disease. We hypothesize that epithelial cell-derived TSLP conditions gastrointestinal dendritic cells to generate Th2-skewed CD4+ T cells that orchestrate the development of food allergy. We will test the mechanism by which TSLP promotes food allergy by a series of adoptive transfer experiments. Next, we will determine the regulation of TSLP in human intestinal epithelial cells cultured in vitro to define potential physiologic triggers that may contribute to food allergic diseases. Understanding what triggers up-regulate TSLP expression could be important for identifying environmental or dietary triggers that promote food allergy. Our third aim will be to generate a transgenic mouse over-expressing TSLP by intestinal epithelial cells. We hypothesize that this transgenic mouse will be susceptible to the development of food allergy, and in addition to providing evidence for a central role of TSLP in food allergy, it would provide a novel murine model of spontaneous food allergy for testing either the allergenicity of food proteins or the efficacy of novel therapeutics.

Cost :$466,125.00

Project IDs:

ID Code :R834064

Project type :EPA Grant