Reducing Luminal Extracellular Adenosine Triphosphate Levels Alleviates Food Allergy Induced by an Egg White Diet in Mice

Abstract

The development of food allergies is typically associated with extensive intestinal inflammation. As a key inflammatory signaling molecule, the precise roles of extracellular adenosine triphosphate in food allergies require further elucidation. Our previous research reported that continuous food allergen exposure led to increased accumulation of luminal extracellular adenosine triphosphate (eATP). In the present study, we demonstrate that the deficient expression of intestinal ENTPD1, an eATP ectoenzyme that can quickly hydrolyze ATP to AMP, likely contributes to the excessive accumulation of luminal eATP in allergic mice. Furthermore, we also illustrate that reducing luminal eATP levels can relieve food allergy manifestations and intestinal inflammation through the effects of lowering local and systemic pro-inflammatory cytokine secretion, diminishing intestinal T helper cell activities, decreasing crosstalk between Tfh cells and B cells in Peyer’s patches, and improving gut dysbiosis. These findings may offer new perspectives for understanding the roles of eATP in food allergies and the mechanisms of food allergy development.