IL-9-Producing Mast Cell Precursors and Food Allergy
Technical Report,30 Sep 2015,29 Sep 2016
Children's Hospital Medical Center Cincinnati United States
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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 antigenIgEFcR complex 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 antigenIgEFcRI 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.
- Medicine and Medical Research