253
Desensitization of Different Subsets of Mast Cells Associated with Different Manifestations of Food Allergy
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Sara Benede, PhD, M. Cecilia Berin, PhD
Rationale: Mast cells are key effector cells of allergic reactions, and are classified into mucosal (MMC) and connective tissue (CTMC) mast cells. We hypothesized that MMC and CTMC could contribute to different clinical manifestations of food allergy, and underlie route-dependent desensitization to foods.

Methods: We evaluated mast cell activation by protease release using two different mouse models of food allergy with gastrointestinal or anaphylaxis symptoms in response to oral challenge. Bone marrow-derived MMC and CTMC were used to study desensitization in vitro.

Results: Using sensitized mice and evaluating those with and without clinical symptoms, we observed that anaphylaxis was significantly associated with CTMC, but not MMC, activation. In contrast, diarrhea was associated with MMC and CTMC activation. Desensitization of anaphylactic mice with oral immunotherapy led to suppression of both MMC and CTMC activation. In vitro sensitization and activation of MMC and CTMC resulted in signaling (phospho-Syk), degranulation (LAMP-1) and cytokine release (IL-6, IL-13 and TNF-α). All activation parameters could be desensitized in both MMC and CTMC.  Extent of desensitization was correlated with extent of initial activation when an antigen-specific system was used (monoclonal DNP-IgE or serum from sensitized mice), and no evidence of bystander desensitization was found. Desensitization of mast cells at a dose below that required for activation was only observed using anti-IgE, and not antigen.

Conclusions: Different manifestations of food allergy are mediated by subsets of mast cells with differing protease profiles. MMC and CTMC show similar potential to become desensitized in vitro, as well as in vivo by an oral route.