The Ectoenzyme E-NPP3 Negatively Regulates ATP-Dependent Chronic Allergic Responses by Basophils and Mast Cells

Summary Crosslinking of the immunoglobulin receptor FceRI activates basophils and mast cells to induce immediate and chronic allergic inflammation. However, it remains unclear how the chronic allergic inflammation is regulated. Here, we showed that ecto-nucleotide pyrophosphatase-phosphodiesterase 3 (E-NPP3), also known as CD203c, rapidly induced by FceRI crosslinking, negatively regulated chronic allergic inflammation. Basophil and mast cell numbers increased in Enpp3 −/− mice with augmented serum ATP concentrations. Enpp3 −/− mice were highly sensitive to chronic allergic pathologies, which was reduced by ATP blockade. FceRI crosslinking induced ATP secretion from basophils and mast cells, and ATP activated both cells. ATP clearance was impaired in Enpp3 −/− cells. Enpp3 −/− P2rx7 −/− mice showed decreased responses to FceRI crosslinking. Thus, ATP released by FceRI crosslinking stimulates basophils and mast cells for further activation causing allergic inflammation. E-NPP3 decreases ATP concentration and suppresses basophil and mast cell activity.