IL-9-Producing Mast Cell Precursors and Food Allergy
Abstract
Food allergy is a harmful immune reaction that occurs shortly after a person eats certain foods, and this disease is becoming significantly more common in developed nations, including the United States. For some people, the reaction to a particular food may merely be uncomfortable. For others, food allergy can trigger a severe or life-threatening allergic reaction called anaphylaxis. This more severe reaction, called food allergy-induced, life-threatening anaphylaxis, is responsible for approximately 30,000 emergency room visits in the United States each year and often has the following symptoms: narrowing of the airways, abdominal pain, diarrhea, vomiting, and/or a severe drop in blood pressure. The bodies of people with food allergy often produce large amounts of an antibody called immunoglobulin E or IgE. IgE binds to a receptor on a type of blood cell called mast cells. These bound IgE can recognize ingested food particles and trigger mast cells to release histamine and/or other substances, which induce the anaphylaxis. Currently, we do not understand why only some individuals with food allergy, rather than all individuals with food allergy, are more prone to develop life-threatening anaphylactic response to ingested food. Our studies of food allergy in mice have uncovered a new type of precursor to mast cells that can produce large amount of an immune protein called interleukin 9, or IL-9. The IL-9 produced amplifies the anaphylactic response to ingested food(s). We called this new cell type "IL-9"-producing mast cell precursors" or "IMCP9" for short. Just as people with food allergy have varying degrees of susceptibility to food allergens, some types, or strains, of mice are also more susceptible to developing severe anaphylactic response to ingested food than others. A survey of strains of mice that do or do not develop food allergy demonstrates that the susceptibility to experimental food allergy is higher in mice with higher numbers of IMCP9 in their small intestine and lower in mice with fewer IMCP9 in their small intestine. It appears that triggering IMCP9 is a key step for mice to gain susceptibility to developing food allergy. Our study is designed to explore the factors that control the development and function of IMCP9. We hope to learn the specifics of how food allergy develops and progresses and to use this information to aid in improved diagnosis and the development of more effective therapies. In particular, we will define the role of an immune protein called interleukin 4, or IL-4, in triggering the increased development of IMCP9. In addition, we will determine whether the binding of the ingested food antigen, IgE, and the receptor on the early mast cell precursors can also trigger the development of IMCP9. Finally, we will identify the human counterpart of IMCP9 and whether the presence of this new cell type, and its unique genetic markers, corresponds with the clinical reactivity of individuals with a history of food allergy. Due to our research team being assembled and experienced and our substantial preliminary data, we expect that the results obtained from this study will meet the objectives within the timeframe of the 3-year grant proposal. The results obtained from these studies will likely greatly influence and improve our conceptual understandings of why some individuals may be more susceptibility to developing food allergy-induced, life-threatening anaphylaxis and thus make possible new designs for medicines to treat and/or prevent food allergy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510517
Entities
People
- Yui Hsi Wang
Organizations
- United States Army