The mechanisms of IL-21 production and follicular B helper T cell (Tfh cell) differentiation

• Project/Area Number: 21790939
• 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: SUTO Akira Chiba University, 大学院・医学研究院, 助教 (50447306)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IL-21 / c-Maf / BTLA / 濾胞ヘルパーT細胞 / Tfh細胞 / Th17細胞

Research Abstract

In this study, we addressed the mechanisms underlying the regulation of IL-21 production in CD4+ T cells. We found that transcription factor c-Maf directly induced IL-21 production in CD4+ T cells by activating IL-21 promoter and enhancer. We also found that BTLA, a third inhibitory co-receptor expressed on B cells and T cells, was highly expressed on follicular B helper T cells (Tfh cells). Moreover, we found that BTLA signaling suppressed IL-21 production from Tfh cells and subsequent Tfh cell-mediated IgG responses.

Research Products

• [Journal Article] B and T lymphocyte attenuator suppresses IL-21 production from follicular helper T cells and subsequent humoral immune responses. (2010)
  • Author(s): Suto A, Kashiwakuma D, Hiramatsu Y, Ikeda K, Takatori H, Suzuki K, Kagami S, Hirose K, Watanabe N, Iwamoto I, Nakajima H.
  • Journal Title: J Immunol. 185 Pages: 2730-2736
  • 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): Suto A, Hiramatsu Y, Kashiwakuma D, Kanari H, Kagami S, Ikeda K, Hirose K, Watanabe N, Grusby MJ, Iwamoto I, Nakajima H.
  • 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, 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] Protective roles of B and T lymphocyte attenuator (BTLA) 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: 127-133
  • Peer Reviewed
• [Journal Article] B and T Lymphocyte Attenuator Suppresses IL-21 Production from Follicular Th Cells and Subsequent Humoral Immune Responses (2010)
  • Author(s): Kashiwakuma D, Suto A, et al.
  • Journal Title: Journal of Immunology Volume: 185 Pages: 2730-2736
  • Peer Reviewed
• [Journal Article] c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-β inhibits c-Maf-induced IL-21 production in CD4+ T cells. (2010)
  • Author(s): Hiramatsu Y, Suto A, et al.
  • Journal Title: Journal of Leukocyte Biology Volume: 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, et al.
  • Journal Title: Int.Arch.Allergy Immunol. Volume: 152
  • Peer Reviewed
• [Journal Article] c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-β inhibits c-Maf-induced IL-21 production in CD4+ T cells (2010)
  • Author(s): Hiramatsu Y, et al
  • Journal Title: Journal of Leukocyte Biology 87 Pages: 703-712
  • Peer Reviewed
• [Journal Article] IL-21 is required for the development of type 1 diabetes in NOD mice. (2009)
  • Author(s): Sutherland AP, Van Belle T, Wurster AL, Suto A, Michaud M, Zhang D, Grusby MJ, von Herrath M.
  • Journal Title: Diabetes. 58 Pages: 1144-1155
  • Peer Reviewed
• [Journal Article] IL-21産生と濾胞ヘルパーT細胞分化の制御機構 (2009)
  • Author(s): 須藤明
  • Journal Title: 細胞工学 28 Pages: 1124-1127
• [Journal Article] STAT6 Inhibits T-bet-independent Thl cell differentiation (2009)
  • Author(s): Tamachi T, Takatori H, Suto A, Nakajima H, et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 382 Pages: 751-755
  • Peer Reviewed
• [Presentation] B and T lymphocyte attenuator suppresses IL-21 production from follicular helper T Cells. (2010)
  • Author(s): D.Kashiwakuma, A.Suto, Y.Hiramatsu, K.Ikeda, S.Kagami, K.Hirose, N.Watanabe, I.Iwamoto, H.Nakajima.
  • Organizer: 14^<th> Internal Congress of Immunology.
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] B and T lymphocyte attenuator suppresses IL-21 production from follicular helper T Cells. (2010)
  • Author(s): Kashiwakuma D, Suto A, et al.
  • Organizer: 14^<th> Internal Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] c-Maf activates the promoter and enhancer of IL-21 gene while TGF- β inhibits c-Maf-induced IL-21 production in CD4+ T cells. (2010)
  • Author(s): Y.Hiramatsu, A.Suto, D.Kashiwakuma, S.Kagami, K.Ikeda, K.Hirose, N.Watanabe, M.Grusby, I.Iwamoto, H.Nakajima.
  • Organizer: 14^<th> Internal Congress of Immunology.
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-24
• [Presentation] BTLA suppresses immunoglobulin production through the modification of Tfh cell function (2009)
  • Author(s): 柏熊大輔、須藤明、渡辺紀彦、中島裕史
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Book] 細胞工学(IL-21産生と濾胞ヘルパーT細胞分化の制御機構)28 (2009)
  • Author(s): 須藤明 中島裕史
  • Publisher: 秀潤社
• [Remarks] ホームページ等
  • URL: http://www.m.chiba-u.ac.jp/class/allergy/kenkyugyouseki.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/allergy/kenkyugyouseki.html
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/publication.html