Immunity 2015-02-17

The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells.

Shih Han Tsai, Makoto Kinoshita, Takashi Kusu, Hisako Kayama, Ryu Okumura, Kayo Ikeda, Yosuke Shimada, Akira Takeda, Soichiro Yoshikawa, Kazushige Obata-Ninomiya, Yosuke Kurashima, Shintaro Sato, Eiji Umemoto, Hiroshi Kiyono, Hajime Karasuyama, Kiyoshi Takeda

Index: Immunity 42(2) , 279-93, (2015)

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Abstract

Crosslinking of the immunoglobulin receptor FcεRI 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 FcεRI 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. FcεRI 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 FcεRI crosslinking. Thus, ATP released by FcεRI crosslinking stimulates basophils and mast cells for further activation causing allergic inflammation. E-NPP3 decreases ATP concentration and suppresses basophil and mast cell activity.Copyright © 2015 Elsevier Inc. All rights reserved.