The Role of IgG in Mouse Models of Food AllergyEPA Grant Number: R834067
Title: The Role of IgG in Mouse Models of Food Allergy
Investigators: Sperling, Anne I. , Bryce, Paul J.
Institution: University of Chicago , Northwestern University
EPA Project Officer: McOliver, Cynthia
Project Period: June 1, 2009 through May 31, 2011
Project Amount: $433,100
RFA: Exploratory Investigations in Food Allergy (2007) RFA Text | Recipients Lists
Research Category: Food Allergy , Health Effects , Health
Food allergy, defined as an adverse immunological response to food, affects more than 11 million Americans and has doubled in incidence between 1997 and 2002. Severe anaphylaxis triggered by reactions to foods is responsible for 150 deaths and more than 30,000 emergency room visits in the United States per year. Despite this impact on health care expenditures, relatively little is known about the risk factors, disease pathogenesis, or the cellular and molecular processes involved in generating food allergy. Unlike other allergic diseases, such as asthma, eczema or rhinitis, food allergy has no current treatments or therapies and patients are left with the only options being strict food avoidance and injectable epinephrine for treatment of responses during accidental exposure. The incidence of food allergy is increasing at an alarming rate, and so research into pathogenesis and treatment is absolutely paramount. The literature supports a central role of the Th2-induced allergen-specific IgE in the pathogenesis of allergic disorders. However, mounting evidence supports the lack of correlation between specific IgE levels and incidence, severity or threshold of responsiveness in food allergy. These findings led us to question the role of allergen-specific IgG in the regulation of Th2 differentiation and the pathogenesis of allergic disorders.
The overall hypothesis of this proposal is that in addition to IgE, antigen-specific IgG also contributes to the pathogenesis of Th2-mediated food allergies by augmenting Th2 immunity and by contributing to the effector responses of anaphylaxis via activation of mast cells and/or macrophages. Dr. Bryce’s group has recently developed an murine model that more accurately mirrors the physical and immunological characteristics of food allergic patients. This animal model development is a breakthrough for research into the allergenicity of pesticide proteins in food. Thus, the overall objective of our proposal is to determine the role of FcγRIII in the development of allergic sensitization in the gut of proteins such as those found in pesticides and its role in the effector phase of allergic symptoms utilizing this novel model.
Dr. Sperling’s group has recently demonstrated that signaling via the activating Fcγ receptor, FcγRIII, in conjunction with TLR stimulation modulated cytokine production from BM dendritic cells and augmented their ability to promote Th2 responses in vitro and in a murine model of asthma. The augmentation of Th2 immunity was distinct and independent of the well established role of FcγRIII in augmenting antigen presentation. Thus, our studies revealed a novel and specific role for FcγRIII signaling in the regulation of T helper cell responses. To address this objective, we propose the following specific aims: Aim #1: Determine the role of FcγRIII signaling on dendritic cells in the induction of food allergy in a novel murine model. Aim #2: Determine the role of IgG-mediated processes on anaphylaxis to oral antigen exposure.
Publications and Presentations:Publications have been submitted on this project: View all 6 publications for this project
Journal Articles:Journal Articles have been submitted on this project: View all 1 journal articles for this project
Supplemental Keywords:allergens, diet, health effects, susceptibility, exposure,
Progress and Final Reports:2009 Progress Report