Grantee Research Project Results
Final Report: Assessment of Allergic Responses to Food Proteins Using a Novel and Sensitive Adjuvant-Free Ingestion-Based Mouse Model
EPA Grant Number: R834825Title: Assessment of Allergic Responses to Food Proteins Using a Novel and Sensitive Adjuvant-Free Ingestion-Based Mouse Model
Investigators: Oettgen, Hans C
Institution: Children’s Hospital, Boston
EPA Project Officer: Aja, Hayley
Project Period: September 15, 2010 through September 14, 2012 (Extended to September 14, 2013)
Project Amount: $424,803
RFA: Approaches to Assessing Potential Food Allergy from Genetically Engineered Plants (2009) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The overall goal of this project was to test the utility of a novel adjuvant-free mouse model of food allergy as a biological probe for food protein allergenicity. We had previously shown that mice harboring and activating mutation of the IL-4 receptor chain (F709) could be sensitized to develop food allergy by ingestion of the model allergen, ovalbumin (OVA). For this EPA STAR project we tested the effects of this mutation on mast cell responses and whether these animals could similarly be sensitized to clinically relevant food allergens (like peanut) and further whether the animals might serve to distinguish allergenic from non-allergenic food proteins. Such an ability to discriminate allergenic from non-allergenic proteins might prove valuable in the analysis of genetically engineered plants.
Summary/Accomplishments (Outputs/Outcomes):
Conclusions:
In a final significant phase of work we have further developed the peanut sensitization protocol in order to elicit more robust immune sensitization and anaphylactic responses. We have shown that intragastric instillation of peanut butter (containing both peanut oils and protein, unlike the protein-only approach initially tried) gives rise to a strong peanut allergy.
The intense expansion of mast cells observed in the peanut treated animals suggested that they play a key role both in immune sensitization and in the anaphylactic response to food allergen. In order to assess this possibility, we undertook the breeding of mast cell-deficient F709 mice by crossing F709 animals with the c-Kit-mutant strain, KitWsh, which completely lacks intestinal mast cells. The mast cell deficient F709 mice showed no anaphylaxis to peanut. In order to prove that mast cells were indeed responsible for this loss of responsiveness, we injected mast cell-deficient F709/KitWsh mice and then subjected them to peanut sensitization and challenge. Mast cell reconstituted mice exhibited robust anaphylactic responses consistent with a central role for mast cells in peanut allergy.
In our most recent experiments on the peanut food allergy model we evaluated the effect of the F709 mutation on the generation of peanut specific regulatory T cells (Treg), cells which are thought to be critical in preventing food allergy under physiologic conditions. By staining for the Treg marker FoxP3 in peanut responsive T cells we found that F709 mice, as expected, have markedly fewer peanut specific Treg than do their wild-type counterparts.
In additional studies under this EPA project, we have worked to determine the most effective and consistent protocol for evaluating the allergenicity of food proteins in F709 mice. We have gathered data for peanut, egg white, rice, and chicken meat proteins using the originally proposed sensitization and challenge protocol.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
Other project views: | All 2 publications | 2 publications in selected types | All 2 journal articles |
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Bartnikas LM, Gurish MF, Burton OT, Leisten S, Janssen E, Oettgen HC, Beaupré J, Lewis CN, Austen KF, Schulte S, Hornick JL, Geha RS, Oyoshi MK. Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis. Journal of Allergy and Clinical Immunology 2013;131(2):451-460.e1-6. |
R834825 (Final) |
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Burton OT, Darling AR, Zhou JS, Noval-Rivas M, Jones TG, Gurish MF, Chatila TA, Oettgen HC. Direct effects of IL-4 on mast cells drive their intestinal expansion and increase susceptibility to anaphylaxis in a murine model of food allergy. Mucosal Immunology 2013;6(4):740-750. |
R834825 (2012) R834825 (2013) R834825 (Final) |
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Supplemental Keywords:
Food allergy, allergen, IgE, anaphylaxis, IL-4Relevant Websites:
http://www.childrenshospital.org/research-and-innovation/research-labs/oettgen-laboratory
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.