TY - JOUR
T1 - The Ectoenzyme E-NPP3 Negatively Regulates ATP-Dependent Chronic Allergic Responses by Basophils and Mast Cells
AU - Tsai, Shih Han
AU - Kinoshita, Makoto
AU - Kusu, Takashi
AU - Kayama, Hisako
AU - Okumura, Ryu
AU - Ikeda, Kayo
AU - Shimada, Yosuke
AU - Takeda, Akira
AU - Yoshikawa, Soichiro
AU - Obata-Ninomiya, Kazushige
AU - Kurashima, Yosuke
AU - Sato, Shintaro
AU - Umemoto, Eiji
AU - Kiyono, Hiroshi
AU - Karasuyama, Hajime
AU - Takeda, Kiyoshi
N1 - Funding Information:
We thank Y. Uno and M. Tajima for generation of Enpp3 −/− mice, T. Kondo and Y. Magota for technical assistance, S. Pareek for critical reading of the manuscript, and C. Hidaka for secretarial assistance. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology , the Japan Science and Technology Agency , and by the Ministry of Health, Labour and Welfare .
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/2/17
Y1 - 2015/2/17
N2 - 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 wasreduced 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.
AB - 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 wasreduced 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.
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U2 - 10.1016/j.immuni.2015.01.015
DO - 10.1016/j.immuni.2015.01.015
M3 - Article
C2 - 25692702
AN - SCOPUS:84923040707
SN - 1074-7613
VL - 42
SP - 279
EP - 293
JO - Immunity
JF - Immunity
IS - 2
ER -
