Analysis of regulation of antigen-specific IgE production in BALT

• Project/Area Number: 20591184
• 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: KAGAMI Shin-ichiro Chiba University, 大学院・医学研究院, 助教 (30375654)
• Co-Investigator(Kenkyū-buntansha): 中島 裕史 千葉大学, 大学院・医学研究院, 教授 (00322024) ; 須藤 明 千葉大学, 大学院・医学研究院, 助教 (50447306)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肺内胚中心様組織 / IL-21 / TFH細胞様細胞 / BTLA / IgE / IgG4関連疾患 / 喘息 / T_<FH>細胞 / CXCR5

Research Abstract

We found that TFH-like cells existed in inducible bronchus-associated lymphoid tissue (iBALT) and expressed high levels of ICOS, PD-1 and BTLA in a murine model of asthma. In addition, we found that TFH-like cells produced a large amount of IL-21 upon TCR stimulation. We also found that patients with IgG4-related lacrimal gland enlargement (LGE) developed asthma-like symptoms. All patients with IgG4-related LGE showed ectopic germinal center-like architecture in lacrimal glands and exhibited elevated serum IgE levels. CD4^+ T cells in patients with IgG4-related LGE exhibited enhanced Th2 cytokine production as compared with those in healthy subjects.

Research Products

• [Journal Article] Role of Th2 cells in IgG4-related lacrimal gland enlargement. (2010)
  • Author(s): Kanari H, Kagami S, Suto A, Iwamoto I, Nakajima H, et al
  • Journal Title: Int Arch Allergy Immunol. 152 Pages: 47-53
  • Peer Reviewed
• [Journal Article] c-Maf activates the promoter and enhancer of IL-21 gene while TGF-b inhibits c-Maf-induced IL-21 expression in CD4^<+> T cells. (2010)
  • Author(s): Hiramatsu Y, Suto A, Kagami S, Nakajima H, et al
  • Journal Title: J Leukoc Biol. 87 Pages: 703-712
  • Peer Reviewed
• [Journal Article] B and T lymphocyte attenuator suppresses IL-21 production from follicular Th cells and subsequent humoral immne responses. (2010)
  • Author(s): Kashiwakuma D, Suto A, Kagami S, Nakajima H, et al
  • Journal Title: J Immunol. 185 Pages: 2730-2736
  • 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, Suto A, Kagami S, Nakajima H, et al
  • Journal Title: J Immunol. 184 Pages: 127-133
  • Peer Reviewed
• [Journal Article] Role of Th2 cells in IgG4-related lacrimal gland enlargement. (2010)
  • Author(s): Kanari H, Kagami S, Suto A, Iwamoto I, Nakajima H, et al
  • Journal Title: Int Arch Allergy Immunol Volume: 152 Pages: 47-53
  • Peer Reviewed
• [Journal Article] B and T lymphocyte attenuator suppresses IL-21 production from follicular Th cells and subsequent humoral immne responses. (2010)
  • Author(s): Kashiwakuma D, Suto A, Kagami S, Nakajima H, et al
  • Journal Title: J Immunol Volume: 1185 Pages: 2730-2736
  • 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, Suto A, Kagami S, Nakajima H, et al
  • Journal Title: J Immunol Volume: 184 Pages: 127-133
  • Peer Reviewed
• [Journal Article] Role of Th2 cells in IgG4-related lacrimal gland enlargement (2010)
  • Author(s): Kanari H, Kagami S, Suto A, Iwamoto I, Nakajima H, et al
  • Journal Title: Int Arch Allergy Immunol (In press)
  • 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, Kagami S, Nakajima H, et al
  • Journal Title: J.Leukoc.Biol. 87 Pages: 703-712
  • Peer Reviewed
• [Journal Article] Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3^<+> regulatory T cells. (2009)
  • Author(s): Kagami S, Suto A, Watanabe N, Iwamoto I, Nakajima H, et al
  • Journal Title: Int Immunol. 21 Pages: 679-689
  • NAID: 40016949809
  • Peer Reviewed
• [Journal Article] STAT6 Inhibits T-bet-independent Th1 cell differentiation. (2009)
  • Author(s): Tamachi T, Takatori H, Kagami S, Nakajima H, et al
  • Journal Title: Biochem Biophys Res Commun. 382 Pages: 751-755
  • Peer Reviewed
• [Journal Article] Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3^+ regulatory T cells (2009)
  • Author(s): Kagami S, Suto A, Watanabe N, Nakajima H, et al
  • Journal Title: Int.Immunol. 21 Pages: 679-89
  • NAID: 40016949809
  • Peer Reviewed
• [Journal Article] Protein geranylgeranylation regulates the balance between Thl7 cells and Foxd3^+ reaulatory T cells (2009)
  • Author(s): Kagami S, Suto A, Watanabe N, Iwamoto I, Nakajima H, et al
  • Journal Title: Int. Immunol (In press)
  • Peer Reviewed
• [Journal Article] Development and characterization of IL-21-producing CD4^<+> T cells. (2008)
  • Author(s): Suto A, Kashiwakuma D, Kagami S, Nakajima H, et al
  • Journal Title: J Exp Med. 205 Pages: 1369-1379
  • NAID: 40016295272
  • Peer Reviewed
• [Journal Article] IL-23 and Th17 cells enhance Th2 cell-mediated eosinophilic airway inflammation in mice. (2008)
  • Author(s): Wakashin H, Hirose K, Kagami S, Nakajima H, et al
  • 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 T cell differentiation and allergic airway inflammation. (2008)
  • Author(s): Furuta S, Kagami S, Suto A, Watanabe N, 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, Watanabe N, Iwamoto I, Nakajima H, et al
  • 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, Suto A, Watanabe N, Nakajima H, et al
  • Journal Title: J. Immunol 180 Pages: 6656-6662
  • Peer Reviewed
• [Journal Article] HMG-CoA reductase inhibitor simvastatin inhibits proinflammatory cvtokine production from murine mast cells (2008)
  • Author(s): Kagami S, Suto A, Watanabe N, Iwamoto I, Nakajima H, et al
  • Journal Title: Int Arch Allergy Immunol 146 Pages: 61-66
  • Peer Reviewed
• [Presentation] 高IgE血症、好酸球増多を伴ったIgG4関連疾患におけるT細胞分化の検討 (2009)
  • Author(s): 加々美新一郎、廣瀬晃一、須藤明、渡邊紀彦、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
  • Year and Date: 2009-10-30
• [Presentation] 高IgE血症、好酸球増多を伴ったIgG4関連疾患におけるT細胞分化の検討 (2009)
  • Author(s): 加々美新一郎、廣瀬晃一、須藤明、渡邊紀彦、中島裕史
  • Organizer: 日本アレルギー学会
  • Place of Presentation: 秋田市
• [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、廣瀬晃一、須藤明、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
  • Year and Date: 2008-12-01
• [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、廣瀬晃一、須藤明、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
• [Book] 臨床・アレルギー科(ゲラニルゲラニル化阻害によるTh17細胞/Treg細胞バランスの制御) (2009)
  • Author(s): 加々美新一郎、金成博子、中島裕史
  • Publisher: 科学評論社
• [Remarks] ホームページ等
  • 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
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/publication.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
  • 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