Accession Number : AD1025208


Title :   IL-9-Producing Mast Cell Precursors and Food Allergy


Descriptive Note : Technical Report,30 Sep 2015,29 Sep 2016


Corporate Author : Children's Hospital Medical Center Cincinnati United States


Personal Author(s) : Wang, Yui Hsi ; Tomar,Sunil ; Shik,Dana ; Smith,Andrew


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1025208.pdf


Report Date : 01 Oct 2016


Pagination or Media Count : 79


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/FcR 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 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.


Descriptors :   Allergic diseases , allergens , anaphylaxis , Food consumption , biological markers , immune system


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE