Investigation of mechanisms by which BTLA inhibit autoimmunity and its application for the treatment of autoimmune diseases

• Project/Area Number: 19591155
• 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 Chiba University, 医学部・附属病院, 講師 (20375653)
• Co-Investigator(Kenkyū-buntansha): HIROSE Kohichi 千葉大学, 医学部・附属病院, 助教 (90400887) ; NAKAJIMA Hiroshi 千葉大学, 大学院・医学研究院, 教授 (00322024)
• Co-Investigator(Renkei-kenkyūsha): HIROSE Kohichi 千葉大学, 医学部・附属病院, 助教 (90400887) ; NAKAJIMA Hiroshi 千葉大学, 大学院・医学研究院, 教授 (00322024)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: BTLA / 副刺激分子 / 自己免疫疾患 / 免疫寛容 / 自己抗体 / NKT細胞 / CD4 T細胞 / ノックアウトマウス / BLTA / CD4T細胞

Research Abstract

最近、我々は新規の抑制性副刺激分子B and T lymphocyte attenuator(BTLA)を同定した。本研究ではBTLAがNKT細胞に発現していることを初めて見出し、BTLA欠損マウスではNKT細胞依存性自己免疫モデルであるconA肝炎が増悪することを明らかにした。すなわち、BTLAがNKT細胞の活性化抑制機能を有し、免疫寛容維持に関与していることを示した。この研究成果は、NKT細胞に発現するBTLAが自己免疫疾患治療の標的となり得ることを示唆しており、BTLAを利用した免疫療法開発に向けた新たな方向性を示せたと考える。

Research Products

• [Journal Article] Development of Autoimmune Hepatitis-like Disease and Autoantibody Production to Nuclear Antigens in Mice Lacking B and T Lymphocyte Attenuator (BTLA) (2008)
  • Author(s): Oya Y, Watanabe N, Hirose K, Suto A, Kagami S-i, Iwamoto I, Nakajima H(他6名)
  • Journal Title: Arthritis Rheum 58 Pages: 2498-2510
  • Peer Reviewed
• [Journal Article] Development and characterization of IL-21-producing CD4^+ T cells (2008)
  • Author(s): Suto A, Kagami S-I, Hirose K, Watanabe N, Iwamoto I, Nakajima H(他5名)
  • Journal Title: J. Exp. Med 205 Pages: 1369-1379
  • NAID: 40016295272
  • 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, Hirose K, Watanabe N, Nakajima H(他5名)
  • Journal Title: J. Immunol 180 Pages: 6656-6662
  • Peer Reviewed
• [Journal Article] Development of Autoimmune Hepatitis-like Disease and Autoantibody Production to Nuclear Antigens in Mice Lacking B and T Lymphocyte Attenuator (BTLA) (2008)
  • Author(s): Oya ay, Watanabe N, Hirise K, Suto A, Kagami S-i, Iwamoto I, Nakajima H, 他6名
  • Journal Title: Arthritis Rheum 58 Pages: 2498-2510
  • Peer Reviewed
• [Journal Article] Development and characterization of IL-21-producing CD4^+ T cells (2008)
  • Author(s): Suto A, Kagami S-I, Hirose K, Watanabe N, Iwamoto I, Nakajima H, 他5名
  • Journal Title: J. Exp. Med. 205 Pages: 1369-1379
  • NAID: 40016295272
  • 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, Hirose K, Watanabe N, Nakajima H, 他5名
  • Journal Title: J. Immunol. 180 Pages: 6656-6662
  • Peer Reviewed
• [Journal Article] Development of Autoimmune Hepatitis-like Disease and Autoantibody Production to Nuclear Antigens in Mice Lacking B and T Lymphocyte Attenuator (BTLA) (2008)
  • Author(s): Oya Y, Watanabe N, Hirose K, Suto A, Kagami S-i, Iwamoto, Nakajima H, (他6名)
  • Journal Title: Arthritis Rheum 58
  • Peer Reviewed
• [Journal Article] Ovellapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic ailway 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] Expressionof 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 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, Watanbe N, Iwamoto I, Nakajima H, (他4名)
  • Journal Title: Blood 110 Pages: 553-560
  • Peer Reviewed
• [Presentation] NKT細胞におけるBTLAの役割 (2008)
  • Author(s): 岩田有史, 渡辺紀彦, 大矢佳寛, 須藤明, 廣瀬晃一, 中島裕史(他5名)
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-01
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/gene/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/index.html