Investigation of mechanisms by which BTLA inhibit autoimmunity and development of potential therapeutic applications

• Project/Area Number: 21591263
• 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: WATANABE Norihiko 千葉大学, 大学院・医学研究院, 准教授 (20375653)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA Hiroshi 千葉大学, 大学院・医学研究院, 教授 (00322024) ; HIROSE Kohichi 千葉大学, 医学部附属病院, 講師 (90400887) ; HANAOKA Hideki 千葉大学, 医学部附属病院, 講師 (80361426)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: BTLA / 副刺激分子 / 自己免疫疾患 / 免疫寛容 / 樹状細胞 / MRL/lprマウス / ノックアウトマウス / 自然免疫 / NKT細胞

Research Abstract

Recently, we have identified B and T lymphocyte attenuator (BTLA) as a novel inhibitory coreceptor expressed on lymphocytes. In this study, we found that the lack of BTLA exaggerates the systemic autoimmunity in lupus-prone MRL-lpr/lpr mice. In addition, we found that BTLA is also expressed on dendritic cells and serves inhibitory functions in dendritic cells. These results demonstrate that BTLA plays a protective role in autoimmune diseases and also suggest potential therapeutic applications of BTLA.

Research Products

• [Journal Article] A functional polymorphism in B and T lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis (2011)
  • Author(s): Oki M, Watanabe N, Owada T, Oya Y, Ikeda Oki M, Watanabe N, Owada T, Oya Y, IkedaK, Nakajima H, 他3名
  • Journal Title: Clin Dev Immunol Pages: 305656-305656
  • Peer Reviewed
• [Journal Article] Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice. (2011)
  • Author(s): Oya Y, Watanabe N, Kobayashi Y, Owada T, Hirose K, Nakajima H, 他5名
  • Journal Title: Int. Immunol Volume: 23 Pages: 335-344
  • Peer Reviewed
• [Journal Article] Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice (2011)
  • Author(s): Oya Y, Watanabe N, Owada T, Oki M, Ikeda K, Suto A, Kagami S-I, Hirose K, Kishimoto T, Nakajima H
  • Journal Title: Int. Immunol Volume: 23 Issue: 5 Pages: 335-44
  • DOI: 10.1093/intimm/dxr017
  • Peer Reviewed
• [Journal Article] A functional polymorphism in B and T lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis (2011)
  • Author(s): Oki M, Watanabe N, Owada T, Oya Y, Ikeda K, Saito Y, Matsumura R, Seto Y, Iwamoto I, Nakajima H
  • Journal Title: Clin. Dev. Immunol Volume: 2011 Pages: 305656-305656
  • DOI: 10.1155/2011/305656
  • Peer Reviewed
• [Journal Article] Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice. (2011)
  • Author(s): Oya Y, Watanabe N, Koba ashi Y, Hirose, K, Nakajima H., 他6名
  • Journal Title: Int.Immunol. Volume: 186 in press
  • Peer Reviewed
• [Journal Article] A functional polymorphism in B and T lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis. (2011)
  • Author(s): Oki M, Watanabe N, Owada T, Ova Y, Nakajima H., 他5名
  • Journal Title: Clin Dev Immunol. Volume: 2011 in press
  • Peer Reviewed
• [Journal Article] Role of Th2 cells in IgG4-related lacrimal gland enlargement (2010)
  • Author(s): Kanari H, Kagami S, Kashiwakuma D, Oya, Hirose K, Watanabe N, Nakajima H, 他7名
  • 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 Immune Responses (2010)
  • Author(s): Kashiwakuma D, Suto A, Hiramatsu Y, Ikeda K, Hirose, K, Watanabe N, Nakajima H, 他4名
  • Journal Title: J. Immunol Volume: 185 Pages: 2730-36
  • Peer Reviewed
• [Journal Article] c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF- inhibits c-Maf-induced IL-21 production in CD4^+ T cells (2010)
  • Author(s): Hiramatsu Y, Suto A, Kashiwakuma D, Hirose K, Watanabe N, Nakajima H, 他6名
  • Journal Title: J Leukoc Biol Volume: 87 Pages: 703-712
  • 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, Hirose K, Nakajima H, 他6名
  • Journal Title: J. Immunol Volume: 184 Pages: 127-133
  • Peer Reviewed
• [Journal Article] Activation-induced Accumulation of B and T Lymphocyte Attenuator at the Immunological Synapse in CD4^+ T Cells (2010)
  • Author(s): Owada T, Watanabe N, Oki M, Oya Y, Murphy KM, Nakajima H, 他4名
  • Journal Title: J Leukoc Biol Volume: 87 Pages: 425-432
  • 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, Hirose, K Watanabe N, Nakajima H., 他6名
  • Journal Title: J.Immunol. Volume: 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, Ikeda K, Suto A, Kagami S, Hirose K, Iwamoto I, Nakajima H., (他6名)
  • Journal Title: J.Immunol. 184 Pages: 127-133
  • Peer Reviewed
• [Journal Article] Activation-induced Accumulation of B and T Lymphocyte Attenuator at the Immunological Synapse in CD4^+ T Cells. (2010)
  • Author(s): Owada T, Watanabe N, Iwamoto I, Nakajima H., (他6名)
  • Journal Title: J Leukoc Biol 87 Pages: 425-432
  • Peer Reviewed
• [Journal Article] c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-inhibits c-Maf-induced IL-21 production in CD4^+ T cells. (2010)
  • Author(s): Hiramatsu Y, Suto A, Kagami S, Ikeda K, Hirose K, Watanabe N, Nakajima H., (他4名)
  • 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-I, Owada T, Kanari H, Hirose K, Watanabe N, Nakajima H, 他4名
  • Journal Title: Int Immunol Volume: 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, Fujiwara M, Hirose K, Watanabe N, Nakajima H, 他4名
  • Journal Title: Biochem Biophys Res Commun Volume: 382 Pages: 751-755
  • Peer Reviewed
• [Presentation] Lack of E and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice. (2011)
  • Author(s): Watanabe N, Oya Y, Ikeda K, Hirose K, Kishimono T, NakaiimaH., 他2名
  • Organizer: 14th International congress of Immunology
  • Place of Presentation: 神戸ポートピアホテル、神戸国際展示場
  • Year and Date: 2011-08-26
• [Presentation] BTLAによる自己免疫応答制御 (2009)
  • Author(s): 渡辺紀彦
  • Organizer: 日本アレルギー学会秋期学術大会
  • Place of Presentation: 秋田キャッスルホテル、秋田ビューホテル、アトリオン
  • Year and Date: 2009-10-30
• [Presentation] BTLAによる自己免疫応答制御 (2009)
  • Author(s): 渡辺紀彦
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田キャッスルホテル
  • Year and Date: 2009-09-30
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/kenkyunaiyou.html
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/project.html
• [Remarks]
  • URL: http://www.m.chiba-u,jb/class/gene/project.html
• [Patent(Industrial Property Rights)] A method of identifying a compound for prevening and/or treating an autoimmune disease (2010)
  • Inventor(s): 渡辺紀彦, 大矢佳寛
  • Industrial Property Rights Holder: 千葉大学
  • Filing Date: 2010-03-30
  • Overseas