Extracellular adenosine triphosphate skews the T helper cells balance and enhances neutrophils activation in mice with food allergy

Abstract

The exposure of food allergens elicits fast changes in the intestinal microenvironment, which guides the development of allergic reactions. Investigating the key information of these changes may help in better understanding food allergy. In this research, we explored the relationship between food allergy and extracellular adenosine triphosphate (ATP), a danger molecule that has been proven to regulate the onset of allergic asthma and dermatitis but has not been studied in food allergy, by building a unique animal model based on allergen-containing diet feeding. After 7-day consumption of an allergen-containing diet, the allergic mice showed severe enteritis with raised luminal ATP levels. The luminal dysregulated ATP deteriorated food-induced enteritis by boosting Th17 cell responses and promoting mucosal neutrophil accumulation. In vitro experiments indicated that the intervention of ATP promoted the differentiation of Th17 cells and the activation of neutrophils. In addition, the diet-induced allergy showed noticeable gut dysbiosis, characterized by decreased microbial diversity and increased diet-specific microbiota signatures. As the first, we show that the food-induced enteritis is associated with an elevated concentration of luminal ATP. The dysregulated extracellular ATP exacerbated the enteritis of mice to food challenge by manipulating intestinal Th17 cells and neutrophils.