Food allergy affects up to 6% of the pediatric population,and up to 3.5% of adults in the United States. Strict allergen avoidance is currently the only approach to the management of food allergy. We have developed a novel immunotherapeutic agent, EMP-123, for the treatment of peanut allergy. We have previously shown that EMP-123 abolishes anaphylaxis in response to oral peanut challenge in peanut-allergic mice. <P> The studies outlined in this application are designed to determine the mechanisms responsible for EMP-123- mediated desensitization to peanut in sensitized mice. We hypothesize that EMP-123 inhibits anaphylaxis by two mechanisms: the induction of antigen-specific regulatory T cells and by modulation of intestinal barrier function. <P> We will first examine innate immune mechanisms of response to EMP-123. We will determine what cells take up EMP-123 encoded antigen, what the impact of the bacterial components are on the phenotype of antigen-bearing cells, and the outcome of interaction between antigen-bearing cells and naive T cells. We will determine the role of host toll-like receptors in sensitization to peanut, and desensitization using EMP- 123. <P> The hypothesis that EMP-123 induces T regulatory cells will be directly tested using cell transfer studies. These studies are designed to comprehensively determine immune mechanisms ofdesensitization to peanut using EMP-123. Another component of the innate immune system is epithelial barrier function, and we hypothesize that EMP-123 treatment results in normalization of barrier function by interfering with sensitization-induced alterations in antigen uptake. We will determine cellular mechanisms of antigen uptake and the role of IgE and CD23-mediated antigen uptake in the context of normal health, peanut sensitization, and desensitization with EMP-123. <P> The results from these studies will identify potential biomarkers tracking the progress of desensitization in humans and will potentially help us to refine EMP-123 for more specific and effective treatment of peanut allergy in humans.
Immunobiology of Food Allergy and Its Resolution
Objective
Investigators
Sampson, Hugh
Institution
Mount Sinai School of Medicine
Start date
2009
End date
2010
Funding Source
Project number
5U19AI066738-05
Categories
Commodities