title: The ectoenzyme E-NPP3 negatively regulates ATP-dependent chronic allergic responses by basophils and mast cells.
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.
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Shih Han
authors.initials: SH
authors.lastname: Tsai
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusu
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Kayama
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Okumura
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takeda
authors.affiliation: Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yoshikawa
authors.affiliation: Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Obata-Ninomiya
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kurashima
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan; Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Electronic address: ktakeda@ongene.med.osaka-u.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000166:cytology / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D003967:Diarrhea / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000276:immunology*; D011755:Pyrophosphatases / Q000235:genetics / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D017455:Receptors, IgE / Q000276:immunology*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: C000597424:E-NPP3 protein, mouse; C546469:P2rx7 protein, mouse; D034741:RNA, Small Interfering; D017455:Receptors, IgE; D058486:Receptors, Purinergic P2X7; D014301:Trinitrobenzenes; D007073:Immunoglobulin E; D000255:Adenosine Triphosphate; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases