Dysfunction of Siglec regulated eosinophilic airway inflammation induce airway remodeling.

• Project/Area Number: 26860596
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Kiwamoto Takumi 筑波大学, 医学医療系, 講師 (80724773)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: Siglec-F / 気道リモデリング / HAS2 / Siglec / Muc5b / Muc4 / 好酸球 / 喘息

Outline of Final Research Achievements

We studied the influence of Siglec pathway on airway remodeling, which is a refractory factor of bronchial asthma. Siglec is a sugar chain-binding protein mainly expressed in inflammatory cells, mouse Siglec-F is mainly expressed on eosinophils. Muc 5b and Muc 4 were identified as ligands for Siglec-F. In addition, the expression level of Siglec-F ligand was increased when airway remodeling was progressed. Hyaluronan synthase HAS2 dysfunction seemed to inhibit the Siglec pathway and may induce refractory asthma.

Research Products

• [Journal Article] Sialylated glycans carried by airway mucins Muc5b and Muc4 selectively bind to mouse Siglec-F and control eosinophilic airway inflammation. (2016)
  • Author(s): Takumi Kiwamoto, Toshihiko Katoh, Christopher M. Evans, Zhou Zhu, Michael Tiemeyer, Bruce S. Bochner
  • Journal Title: Proceedings of the 30th Symposium of the Collegium Internationale Allergologicum. Volume: - Pages: 29-32
  • Int'l Joint Research
• [Journal Article] Reply: To PMID 25497369. (2015)
  • Author(s): Bruce S. Bochner, Takumi Kiwamoto, Toshihiko Katoh, Zhou Zhu, Michael Tiemeyer
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 135 Issue: 6 Pages: 1662-3
  • DOI: 10.1016/j.jaci.2015.02.028
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis. (2015)
  • Author(s): Takumi Kiwamoto, Toshihiko Katoh, Christopher M. Evans, William J. Janssen, Mary E. Brummet, Sherry A. Hudson, Zhou Zhu, Michael Tiemeyer, Bruce S. Bochner
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 135 Issue: 5 Pages: 1329-40
  • DOI: 10.1016/j.jaci.2014.10.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Siglec-Fとムチン相互作用による好酸球炎症制御 (2015)
  • Author(s): 加藤 紀彦, 際本 拓未
  • Journal Title: The lung perspectives Volume: 23 Pages: 180-185
• [Journal Article] Siglecとアレルギー性気道炎症制御 (2015)
  • Author(s): 際本 拓未, 檜澤 伸之
  • Journal Title: 雑誌「呼吸」 Volume: 34 Pages: 21-24
• [Presentation] Attenuation of Hyaluronan synthase 2 (HAS2) enhance eosinophilic airway inflammation. (2017)
  • Author(s): Yoshiya Tsunoda, Takumi Kiwamoto, Hirofumi Sakurai, Lin Shin-Yuan, Yosuke Matsuno, Mio Kawaguchi, Yuko Morishima, Yukio Ishii, Nobuyuki Hizawa
  • Organizer: ATS International Conference 2017
  • Place of Presentation: ワシントンDC(米国)
  • Int'l Joint Research
• [Presentation] 好酸球性気道炎症病態下におけるヒアルロン酸合成酵素HAS2の役割 (2017)
  • Author(s): 角田 義弥、際本 拓未、櫻井 啓文、林 士元、松野 洋輔、川口 未央、森島 祐子、石井 幸雄、檜澤 伸之
  • Organizer: 第57回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム(東京都、千代田区)
• [Presentation] Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis. (2015)
  • Author(s): Takumi Kiwamoto, Toshihiko Katoh, Christopher M. Evans, William J. Janssen, Mary E. Brummet, Sherry A. Hudson, Zhou Zhu, Michael Tiemeyer, Bruce S. Bochner
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪 国際館パミール
  • Year and Date: 2015-05-26
• [Presentation] Mouse airway Muc5b and Muc4 carry glycans that induce eosinophil apoptosis via Siglec-F. (2015)
  • Author(s): Takumi Kiwamoto, Toshihiko Katoh, Christopher M. Evans, William J. Janssen, Mary E. Brummet, Sherry A. Hudson, Zhou Zhu, Michael Tiemeyer, Bruce S. Bochner
  • Organizer: 2015 KAAACI & EAAS Joint International Congress
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2015-05-08
  • Int'l Joint Research
• [Presentation] Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis (2014)
  • Author(s): Kiwamoto T, Katoh T, Evans CM, Janssen WJ, Brummet ME, Hudson SA, Zhu Z, Tiemeyer M, Bochner BS.
  • Organizer: SFG & JSCR 2014 Joint Annual Meeting
  • Place of Presentation: 米国（ホノルル）
  • Year and Date: 2014-11-17
• [Presentation] 気道粘液Muc5b/Muc4によるSiglec-Fを介した好酸球炎症制御機構 (2014)
  • Author(s): 際本 拓未, 加藤 紀彦, Christopher Evans, Mary Brummet, Sherry Hudson, Zhou Zhu, Michael Tiemeyer, Bruce Bochner
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-25