TAKEDA Kiyoshi ≪Immune Regulation≫ “The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells”
Mast cells and basophils play mandatory roles in the pathogenesis of allergic diseases, such as bronchial asthma and atopic diseases. However, it remain unclear how the activity of mast cells/basophils are regulated. We analyzed the function of E-NPP3 (CD203c), which is highly expressed in activated basophils. Mast cells/basophils increased in number and are highly activated in mice lacking E-NPP3. Accordingly, E-NPP3-deficient mice suffered from severe skin allergic inflammation, allergic diarrhea, and bronchial asthma. Mast cells/basophils were shown to secrete adenosine triphosphate (ATP) upon activation. In E-NPP3-deficient mast cells/basophils, ATP level was increased and ATP activated E-NPP3-deficient mast cells/basophils in an autocrine manner, leading to development of severe allergic inflammation. Thus, E-NPP3 suppresses the ATP-dependent activation of mast cells/basophils, and thereby negatively regulates allergic responses.