UDP-glucose exacerbates egg white diet-induced allergic enteritis by promoting P2Y14-mediated neutrophil chemotaxis in mice

Abstract

While numerous studies have reported that exposure to food allergens can increase neutrophil counts in peripheral blood and the gastrointestinal tract, the specific roles of neutrophils in food allergy development remain unclear. By feeding an egg white diet, we investigated the contribution of neutrophil infiltration to food allergy development and explored the mechanisms driving neutrophil activity. Our results demonstrated that neutrophil depletion significantly reduced the secretion of inflammatory cytokines. Additionally, mice with food allergies exhibited widespread intestinal epithelial pyroptosis mediated by caspase-3 and Gsdmc, which subsequently promoted the release of UDP-glucose (UDPG) into the extracellular space. Increased levels of UDPG activated P2Y14R expressed on the surface of neutrophils, facilitating their chemotaxis to inflamed sites. Inhibition of P2Y14R significantly diminished mucosal neutrophil infiltration, thereby alleviating food allergy symptoms and intestinal damage in mice. We believe our findings may provide new insights for investigating the mechanisms underlying food allergy development.