IL-9-Producing Mast Cell Precursors and Food Allergy
Abstract
Food allergy is a harmful immune reaction driven by uncontrolled type-2 immune responses. Current knowledge provide limited insights into why only some, rather than all food allergic individuals are prone to develop life-threatening anaphylaxis. We have identified a novel multi-functional IL-9-producing mucosal mast cells (MMC9s) that produce large amounts of IL-9, IL-13, and mast cell mediators. The objective of this proposal is to identify the factors that regulate MMC9 induction, which represents the key cellular checkpoint to develop food-induced anaphylaxis. The central hypothesis is that signals induced by IL-4 and antigen/IgE/FcRcomplex crosslinking act together to induce mast cell (MC) progenitors to develop into the pathogenic MMC9s, which amplify anaphylactic response to dietary allergens. We have established genetically modified murine strains, a new reconstitution model of experimental food allergy, and the system to acquire duodenal biopsy samples from food allergic patients. Preliminary evidences show that both IL-4 and antigen/IgE/FcRI complex are essential for MMC9 development. The findings provide a plausible view that the combinatorial signals from atopic status and dietary allergen ingestions can induce aberrant MMC9 development, resulting in the susceptibility to life-threatening anaphylaxis. The impact from these studies may facilitate the discovery of biomarkers and therapeutic targets for diagnosing, preventing, and treating food allergy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1047654
Entities
People
- Andrew N. Smith
- Dana Shik
- Simon P Hogan
- Sunil Tomar
- Yui H. Wang