Epithelial barrier function in skin-gut crosstalk in a model of food allergy 2260278

Abstract

Abstract Introduction Food allergy is a worldwide public health issues that continues to grow every year. However, diagnosis is difficult, as the only way to definitively diagnose a food allergy is through oral food challenge. This is time consuming and often results in anxiety as adverse reactions, including anaphylaxis, are common. Previous data found that children who develop severe reactions during oral food challenges have an increase in transepidermal water loss (TEWL) prior to reacting, indicating that TEWL may help to predict which patients will react. Methods We used a mouse model of food allergy to better understand the interplay between skin barrier function and anaphylactic reactions. Animals were dermally sensitized with ovalbumin, then challenged by oral gavage. Transepidemal water loss was measured before and after challenge. Small intestinal tissue was collected following challenge to evaluate mast cell density and cytokine expression. Results We found mice accumulated mast cells in the small intestine, and that this correlated with increased transepidermal waters loss (TEWL). We also measured an increase in the expression Th2-associated alarmins in the intestinal tissue, including IL-33 and TSLP. These effects were enhanced in mice with genetic barrier defects, indicating a potential link between intestinal mast cell accumulation and skin barrier function. Additionally, we found that mice with barrier defects had increased TEWL prior to skin sensitization, suggesting that skin barrier function may play a role in the severity of food allergy. Conclusion This model will provide us with a platform to explore the mechanisms behind increased TEWL observed in patients during oral food challenge, and may lead to better diagnoses of food allergy. Funding Source R01 AI 167957 Topic Categories Mucosal and Regional Immunology (MUC)