Barrier function facilitates cross-talk between skin and intestine in a model of food allergy 3054

Abstract Description The incidence of food allergy has increased dramatically over the last several decades, along with several other allergic diseases, including atopic dermatitis. Infants with severe atopic dermatitis are more likely to develop food allergies during childhood, and the role of skin in sensitization to food allergens is currently an area of great interest. We have previously found that mice lacking Junctional Adhesion Molecule A (JAM-A) have a leaky intestinal epithelium and a more severe response in a model of food allergy using systemic sensitization, primarily due to increased Th2 inflammation and accumulation of mast cells in the intestine. As JAM-A is also expressed in keratinocytes, we hypothesized that these mice would have a more pronounced response in a skin sensitization model of food allergy. We found that JAM-A-/- mice have increased expression of IL-33 and TSLP in the skin following epidermal disruption compared to WT C57BL/6 mice, resulting in an increase in mast cells in the small intestine. Allergen sensitization through the skin lead to increased responses to oral challenge as measured by mast cell accumulation and Th2 cytokine production from intestinal tissue and mesenteric lymph nodes. Finally, sensitization through either systemic or dermal routes lead to increased skin permeability following oral challenge. Together, our results suggest an important role for barrier function in the cross-talk between the skin and gut in allergic disease. Funding Sources Supported by NIH/NIAID R01 AI167957, Michigan Food Allergy Research Accelerator Pilot Grant Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)