title: E-NPP3 controls plasmacytoid dendritic cell numbers in the small intestine.
abstract: Extracellular adenosine 5'-triphosphate (ATP) performs multiple functions including activation and induction of apoptosis of many cell types. The ATP-hydrolyzing ectoenzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 3 (E-NPP3) regulates ATP-dependent chronic allergic responses by mast cells and basophils. However, E-NPP3 is also highly expressed on epithelial cells of the small intestine. In this study, we showed that E-NPP3 controls plasmacytoid dendritic cell (pDC) numbers in the intestine through regulation of intestinal extracellular ATP. In Enpp3-/- mice, ATP concentrations were increased in the intestinal lumen. pDC numbers were remarkably decreased in the small intestinal lamina propria and Peyer's patches. Intestinal pDCs of Enpp3-/- mice showed enhanced cell death as characterized by increases in annexin V binding and expression of cleaved caspase-3. pDCs were highly sensitive to ATP-induced cell death compared with conventional DCs. ATP-induced cell death was abrogated in P2rx7-/- pDCs. Accordingly, the number of intestinal pDCs was restored in Enpp3-/- P2rx7-/- mice. These findings demonstrate that E-NPP3 regulates ATP concentration and thereby prevents the decrease of pDCs in the small intestine.
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.|Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoki
authors.initials: Y
authors.lastname: Furuta
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, 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, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, 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, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, 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, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.|Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kurashima
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.|Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, 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, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: C000597424:E-NPP3 protein, mouse; D000255:Adenosine Triphosphate; D010727:Phosphoric Diester Hydrolases; D053148:Caspase 3; D011755:Pyrophosphatases