Role of IL-17 family cytokines in severe asthma

• Project/Area Number: 19591156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Chiba University
• Principal Investigator: NAKAJIMA Hiroshi Chiba University, 大学院・医学研究院, 教授 (00322024)
• Co-Investigator(Kenkyū-buntansha): SUTO Akira 千葉大学, 大学院・医学研究院, 助教 (50447306) ; WATANABE Norihiko 千葉大学, 医学部・附属病院, 講師 (20375653)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 気管支喘息 / 難治化 / IL-17 / IL-23 / Th17細胞 / IL-25 / STAT6 / T-bet / STAT4

Research Abstract

アレルギー性気道炎症におけるIL-23-Th17細胞経路の役割を解析し、IL-23はアレルギー性気道炎症の局所において産生され、Th17細胞の分化と好中球性炎症を誘導するとともに、Th2細胞による好酸球性炎症にも促進的に作用すること、一方、Th17細胞自体もIL-17A非依存的な機構でTh2細胞により誘導される好酸球性気道炎症を増強することを明らかにした。近年、Th17細胞依存性気道炎症はステロイド抵抗性であることが示されており、IL-23-Th17細胞経路は喘息の重症化/難治化との関係が示唆される。本研究成果により、喘息患者におけるIL-23-Th17細胞経路の役割の解明が進み、重症喘息の新規治療法開発へと進展することが期待される。

Research Products

• [Journal Article] Development of autoimmune hepatitis-like disease and production of autoantibodies to nuclear antigens in mice lacking B and T lymphocyte attenuator (2008)
  • Author(s): Oya Y, Watanabe N, Owada T, Oki M, HiroseK, Suto A, Kagami S-i, Nakajima H, Kishimoto T, Iwamoto I, Murphy TL, Murphy KM, Saito Y
  • Journal Title: Arthritis Rheum 58 Pages: 2498-2510
  • Peer Reviewed
• [Journal Article] HMG-CoA reductase inhibitor simvastatin inhibits proinflammatory cytokine production from murine mast cells (2008)
  • Author(s): Kagami S-i, Kanari H, Suto A, Fujiwara M, Ikeda K, Hirose K, Watanabe N, Iwamoto I, Nakajima H.
  • Journal Title: Int. Arch. Allergy Immunol 146 Pages: 61-66
  • Peer Reviewed
• [Journal Article] Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation (2008)
  • Author(s): Furuta S, Kagami S-I, Tamachi T, Ikeda K, Fujiwara M. Suto A, Hirose K, Watanabe N, Saito Y, Iwamoto I, Nakajima H
  • Journal Title: J. Immunol 180 Pages: 6656-6662
  • Peer Reviewed
• [Journal Article] Development and characterization of IL-21-producing CD4^+ T cells (2008)
  • Author(s): Suto A, Kashiwakuma D, Kagami S-I, Hirose K, Watanabe N, Yokote K, Saito Y, Nakayama T, Grusby MJ, Iwamoto I, Nakajima H
  • Journal Title: J. Exp. Med 205 Pages: 1369-1379
  • NAID: 40016295272
  • Peer Reviewed
• [Journal Article] GS143, an IκB ubiquitination inhibitor, inhibits allergic airway inflammation in mice (2008)
  • Author(s): Hirose K, Wakashin H, Oki M, Kagami S-I,Suto A, Ikeda K, Watanabe N, Iwamoto I, Furuichi Y, Nakajima H
  • Journal Title: Biochem Biophys Res Commun 347 Pages: 507-511
  • Peer Reviewed
• [Journal Article] IL-23 and Th17 cells enhance Th2 cell-mediated eosinophilic airway inflammation (2008)
  • Author(s): Wakashin H, Hirose K, Maezawa Y, Kagami S-I, Suto A, Watanabe N, Saito Y, Hatano M, Tokuhisa T, Iwakura Y, Puccetti P, Iwamoto I, Nakajima H
  • Journal Title: Am. J. Respir. Crit. Care Med 178 Pages: 1023-1032
  • Peer Reviewed
• [Journal Article] A novel subset ofmouse NKT cells bearing the IL-17 receptor Bresponds to IL-25 and contributes to airway hyperreactivity (2008)
  • Author(s): Terashima A, Watarai H, Inoue S, Sekine E, Nakagawa R, Hase K, Iwamura C, Nakajima H, Nakayama T, Taniguchi M
  • Journal Title: J. Exp. Med 205 Pages: 2727-2733
  • Peer Reviewed
• [Journal Article] Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation (2008)
  • Author(s): Furuta S, kagami S-I, Suto A, Watanabe N, Nakajima H, et al
  • Journal Title: J. Immunol 180 Pages: 6656-6662
  • Peer Reviewed
• [Journal Article] A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. (2008)
  • Author(s): Terashima A, Watarai H, Nakajima H, Taniguchi M, et al
  • Journal Title: J. Exp. Med 205 Pages: 2727-2733
  • Peer Reviewed
• [Journal Article] IL-23 and Th17 cells enhance Th2 cell-mediated cosinophilic airway inflammation in mice. (2008)
  • Author(s): Wakashin H, Hirose K, Kagami S-I, Suto A, Nakajima H.
  • Journal Title: Am. J. Respir. Crit. Care Med. 178 Pages: 1023-1032
  • Peer Reviewed
• [Journal Article] Overlapping and distinct roles of STAT4 and T-bet in the regulation of cell differentiation and alleric airwa inflammation (2008)
  • Author(s): Furuta S, Kagami S, Hirose K, Watanabe N, Nakajima H, (他5名)
  • Journal Title: J.Immunol 180(in press)
  • Peer Reviewed
• [Journal Article] T-bet inhibits both Th2 cell-mediated eosinophil recruitment and Th17 cell-mediated neutrophil recruitment into theairways (2007)
  • Author(s): Fujiwara M, Hirose K, Kagami S-I, Takatori H, Wakashin H, Tamachi T, Watanabe N, Saito Y, Iwamoto I, Nakajima H
  • Journal Title: J. Allergy Clin. Immunol 119 Pages: 662-670
  • Peer Reviewed
• [Journal Article] BTLA inhibits antigen-induced eosinophil recruitment into the airways (2007)
  • Author(s): Tamachi T, Watanabe N, Oya Y, Kagami S-I, Hirose K, Saito Y, Iwamoto I, Nakajima H
  • Journal Title: Int. Arch. Allergy Immunol 143
  • Peer Reviewed
• [Journal Article] Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation (2007)
  • Author(s): Tokumasa N, Suto A, Kagami S-i, Furuta S, Hirose K, Watanabe N, Saito Y, Shimoda K, Iwamoto I, Nakajima H
  • Journal Title: Blood 110 Pages: 553-560
  • Peer Reviewed
• [Journal Article] Expression of Tyk2 in dendritic cells is required for IL-12,IL-23,and IFN-γ production and the induction of Th1 cell differentiation (2007)
  • Author(s): Tokumasa N, Suto A, Kagami S-i, Watanabe N, Iwamoto I, Nakajima H, (他4名)
  • Journal Title: Blood 100 Pages: 553-560
  • Peer Reviewed
• [Journal Article] T-bet inhibits both Th2 cell-mediated eoslnophil recmitment and Th17 cell-mediated neutrophil recruitment into the airways (2007)
  • Author(s): Fujiwara M, Hirose K, Watamabe N, Saito Y, Iwamoto I, Nakajima H, (他4名)
  • Journal Title: J.Allergy Clin.Immunol 119 Pages: 662-670
  • Peer Reviewed
• [Journal Article] Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3^+ regulatory T cells
  • Author(s): Kagami S, Owada T, Kanari H, Saito Y, Suto A, Ikeda K, Hirose K, Watanabe N, Iwamoto I, Nakajima H
  • Journal Title: Int. Immunol (in press)
  • NAID: 40016949809
  • Peer Reviewed
• [Presentation] IL-23-Th17細胞経路とアレルギー性気道炎症 (2009)
  • Author(s): 中島裕史
  • Organizer: 第27回日本耳鼻咽喉科免疫アレルギー学会教育講演
  • Place of Presentation: 千葉
• [Presentation] 抗原誘導性気道炎症におけるIL-23およびTh17細胞の役割の解明 (2008)
  • Author(s): 廣瀬晃一, 若新英史, 渡辺紀彦, 中島裕史
  • Organizer: アレルギー好酸球研究会2008
  • Place of Presentation: 東京
  • Year and Date: 2008-06-21
• [Presentation] アレルギー性気道炎症に対するIκB特異的ユビキチン化阻害剤の効果の検討 (2008)
  • Author(s): 廣瀬晃一、若新英史、池田啓、須藤明、加々美新一郎、渡邊紀彦、中島裕史
  • Organizer: 第58回日本アレルギー学会
  • Place of Presentation: 東京
• [Presentation] アレルギー性炎症機序解明における将来展望抗原誘発性気道炎症におけるIL-23/Th17細胞経路の役割 (2008)
  • Author(s): 若新英史、廣瀬晃一、池田啓、須藤明、渡邊紀彦、加々美新一郎、岩本逸夫、中島裕史
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] NKT細胞におけるBTLAの役割 (2008)
  • Author(s): 岩田有史、渡邊紀彦、大和田高義、大矢佳寛、須藤明、加々美新一郎、廣瀬晃一、中山俊憲、中島裕史
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Th17細胞及びFoxP3陽性細胞分化に対するHMG-CoA還元酵素阻害剤の作用 (2008)
  • Author(s): 加々美新一郎、大和田高義、須藤明、廣瀬晃一、渡邊紀彦、中島裕史
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] CD4陽性T細胞におけるIL-21産生制御機構 (2008)
  • Author(s): 柏熊大輔、須藤明、岩本逸夫、中島裕史
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Development and Characterization of IL-21-producing CD4+ T Cells (2008)
  • Author(s): 中島裕史
  • Organizer: 第4回日本免疫学会(JSI)-理研免疫アレルギーセンター(RCAI)免疫ワークショップ
  • Place of Presentation: 山梨
• [Presentation] Role of T-bet in the regulation of allergic airway inflammation (2007)
  • Author(s): Hiroshi Nakajima
  • Organizer: World Allergy Congress
  • Place of Presentation: Bangkok,Thailand
  • Year and Date: 2007-12-06
• [Presentation] T-betおよびSTAT6によるヘルパーT細胞分化制御機構の解明 (2007)
  • Author(s): 玉地智宏、藤原道雄、高取宏昌、廣瀬晃一、須藤明、加々美新一郎、渡邊紀彦、齋藤康、岩本逸夫、中島裕史
  • Organizer: 第57回日本アレルギー学会
• [Presentation] アレルギー性気道炎症におけるStat4とT-betの役割の解明 (2007)
  • Author(s): 古田俊介、加々美新一郎、須藤明、廣瀬晃一、渡邊紀彦、岩本逸夫、中島裕史
  • Organizer: 第37回日本免疫学会
• [Presentation] 抗原誘発性気道炎症におけるIL-17およびIL-23の役割の解明 (2007)
  • Author(s): 若新英史、廣瀬晃一、渡邊紀彦、加々美新一郎、幡野雅彦、岩本逸夫、岩倉洋一郎、徳久剛史、中島裕史
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 横浜
• [Book] 臨床免疫・アレルギー科(50) (2008)
  • Author(s): 若新英史、廣瀬晃一、中島裕史
  • Publisher: アレルギー性気道炎症におけるIL-23とTh17細胞の役割
• [Book] 医学のあゆみ(227) (2008)
  • Author(s): 須藤明、中島裕史
  • Publisher: CD4陽性T細胞におけるIL-21産生制御機構
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/publication.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/gene/publication.html
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/index.html
• [Patent(Industrial Property Rights)] ゲラニルゲラニル化阻害による制御性T細胞の分化誘導およびその治療応用 (2009)
  • Inventor(s): 中島裕史、加々美新一郎、須藤明、金成博子
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 2009-029880
  • Filing Date: 2009-02-12
• [Patent(Industrial Property Rights)] ゲラニルゲラニル化阻害による制御性T細胞の分化誘導およびその治療応用 (2009)
  • Inventor(s): 中島裕史, 加々美新一郎, 須藤明, 金成博子
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 2009-029880
  • Filing Date: 2009-02-12