The molecular mechanism of IL-25-mediated allergic airway inflammation

• Project/Area Number: 20790688
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Chiba University
• Principal Investigator: IKEDA Kei Chiba University, 医学部・附属病院, 助教 (10456014)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IL-25 / 気管支喘息 / アレルギー性炎症 / ヘルパーT細胞分化 / 肺血管リモデリン / 肺血管リモデリング / CD4

Research Abstract

We showed that IL-25 expression is increased in the airway of experimental mouse model of asthma and that neutralization of IL-25 by soluble IL-25 receptor-Fc fusion protein suppresses eosinophilic inflammation in experimental mouse model of asthma. We also established intracellular IL-25 staining method using soluble IL-25 receptor-Fc fusion protein and has found that the cytokine profile of IL-25 producing CD4+T cells is not identical to that of Th2 cells. Furthermore, we found that the lung-specific IL-25 expression not only exacerbates allergic airway inflammation, but also induces pulmonary arteriolitis and marked remodeling of vascular wall, which is now under detailed investigation.

Research Products

• [Journal Article] Role of Th2 cells in IgG4-related lacrimal gland enlargement. (2010)
  • Author(s): Kanari H, Kagami S, Kashiwakuma D, Oya Y, Furuta S, Ikeda K, Suto A, Suzuki K, Hirose K, Watanabe N, Okamoto Y, Yamamoto S, Iwamoto I, Nakajima H.
  • Journal Title: Int. Arch. Allergy Immunol 152
  • Peer Reviewed
• [Journal Article] c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-{beta} inhibits c-Maf-induced IL-21 production in CD4+T cells. (2010)
  • Author(s): Hiramatsu Y, Suto A, Kashiwakuma D, Kanari H, Kagami SI, Ikeda K, Hirose K, Watanabe N, Grusby MJ, Iwamoto I, Nakajima H.
  • Journal Title: J. Leukoc. Biol. 87 Pages: 703-12
  • Peer Reviewed
• [Journal Article] Protective roles of B and T lymphocyte attenuator in NKT cell-mediated experimental hepatitis. (2010)
  • Author(s): Iwata A, Watanabe N, Oya Y, Owada T, Ikeda K, Suto A, Kagami S, Hirose K, Kanari H, Kawashima S, Nakayama T, Taniguchi M, Iwamoto I, Nakajima H.
  • Journal Title: J. Immunol 184 Pages: 127-33
  • Peer Reviewed
• [Journal Article] Protective roles of B and T lymphocyte attenuator in NKT cell-mediated experimental hepatitis (2010)
  • Author(s): Iwata A, Watanabe N, Ikeda K, Hirose K, et al.
  • Journal Title: J Immunol 184 Pages: 127-133
  • Peer Reviewed
• [Journal Article] c-Maf activates the promoter and enhancer of IL-21 gene while TGF-β inhibits c-Maf-induced IL-21 expression in CD4^+ T cells (2010)
  • Author(s): Hiramatsu Y, Suto A, Ikeda K, Nakajima H, et al
  • Journal Title: J.Leukoc.Biol. 87 Pages: 703-712
  • Peer Reviewed
• [Journal Article] Role of Th2 cells in IgG4-related lacrimal gland enlargement (2010)
  • Author(s): Kanari H, Kagami S, Suto A, Ikeda K, Nakajima H, et al
  • Journal Title: Int Arch Allergy Immunol (in press)
  • Peer Reviewed
• [Journal Article] Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3+ regulatory T cells. (2009)
  • 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 21 Pages: 679-89
  • Peer Reviewed
• [Journal Article] Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3^+ regulatory T cells (2009)
  • Author(s): Kagami S, Suto A, Ikeda K, Watanabe N, Iwamoto I, et.al.
  • Journal Title: Int. Immunol. (In press)
  • 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: 6656-62
  • 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: 61-6
  • Peer Reviewed
• [Journal Article] GS143, an IKB 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. 374 Pages: 507-11
  • 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, Ikeda K, Nakajima H, et.al.
  • Journal Title: J. Immunol. 180 Pages: 6656-6662
  • Peer Reviewed
• [Journal Article] HMG-CoA reductase inhibitor simvastatin inhibits proinflammatory cytokine production from murine mast cells (2008)
  • Author(s): Kagami S, Suto A, Ikeda K, Iwamoto I, Nakajima H, et.al.
  • Journal Title: Int Arch Allergy Immunol 146 Pages: 61-66
  • Peer Reviewed
• [Presentation] 当院で治療したアレルギー性肉芽腫性血管炎の臨床的解析 (2009)
  • Author(s): 池田啓、若新英史、大矢佳寛、中島裕史
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田ビューホテル
  • Year and Date: 2009-10-30
• [Presentation] 当院で治療したアレルギー性肉芽腫性血管炎の臨床的解析 (2009)
  • Author(s): 池田啓、若新英史、大矢佳寛、中島裕史, 他
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-30
• [Presentation] 当院で経験したIgG4関連疾患7例の検討 (2009)
  • Author(s): 横田雅也、加々美新一郎、池田啓、岩田有史、大矢佳寛、須藤明、廣瀬晃一、渡邊紀彦、中村洋介、山本修一、岡本美孝、中島裕史
  • Organizer: 第106回日本内科学会総会・講演会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2009-04-10
• [Presentation] 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: 東京国際フォーラム
  • Year and Date: 2008-11-27
• [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、中島裕史、他
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-27
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/publication.html
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/publication.html
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/publication.html