Role of epithelial barrier function in food-induced anaphylaxis

Role of epithelial barrier function in food-induced anaphylaxis ABSTRACT Food allergy is a growing public health problem with approximately 15 million people affected in the United States. In allergic food disease, IgE on mast cells bind to ingested antigens leading to the activation and degranulation of mast cells. In order to activate mast cells, food antigens must pass through the intestinal epithelial barrier and activate cells in the lamina propria. Junction Adhesion Molecule-A (JAM-A) is a tight junction transmembrane protein that plays a major role in the maintenance of barrier function in epithelia and endothelia. In the small intestine, JAM-A has been shown to be important in epithelial barrier function, and mice that lack JAM-A (JAM-A-/-) have increased intestinal permeability. These JAM-A-/- mice develop severe food allergic disease compared to WT animals and have increased mast cells in the lamina propria of the small intestine, as well as increased activation of these cells. In this proposal, we aim to better understand the role of JAM-A in the development of severe food allergy, including the induction of a strong Th2 response that results in mast cell accumulation in the small intestine. We further plan to target those mast cells in susceptible animals with the aim of decreasing the allergic response. To do this, we will neutralize stem cell factor (SCF), a cytokine that is required for the growth and activation of peripheral tissue mast cells. We hypothesize that neutralizing SCF will prevent mast cell accumulation and protect from severe anaphylactic reactions. These experiments will contribute to our understanding of barrier function in food allergic reactions, as well as provide a potential method for decreasing these reactions in the presence of a dysregulated barrier.