ldentification of pathogenicity determining factors of desmoglein3-reactive T cells and evaluation of its blockade therapy.

• Project/Area Number: 19790801
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: TAKAHASHI Hayato Keio University, 医学部, 助教 (40398615)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 天疱瘡 / 免疫学 / T細胞

Research Abstract

尋常性天疱瘡(PV)において病態と関連する抗デスモグレイン3(Dsg3)抗体の産生にはDsg3を認識する自己反応性T細胞の関与が推測されている。そこで、PVモデルマウスを利用し、Dsg3反応性T細胞の特性を解析した。まずDsg3反応性T細胞株を樹立し、このT細胞株の中にはPVを誘導できる病原性の有る株と無い株が存在することを明らかにした。さらにこの病原性にとってIL-4が重要な分子であり、IL-4を阻害することによりPV発現型が抑制されることを示した。以上よりIL-4を標的とする新規治療法の可能性を示した。

Research Products

• [Journal Article] A Single Helper T cell Clone Is Sufficient to Commit Polyclonal Naive B cells to Produce Pathogenic IgG in Experimental Pemphigus Vulgaris (2009)
  • Author(s): Takahashi H, Kuwana M, Amagai M
  • Journal Title: J Immunol 182(3) Pages: 1740-1745
  • Peer Reviewed
• [Journal Article] Novel System Evaluating In Vivo Pathogenicity of Desmoglein 3-Reactive T-Cell Clones Using Murine Pemphigus Vulgaris (2008)
  • Author(s): Takahashi H, Amagai M, Nishikawa T, Fujii Y, Kawakami Y, Kuwana M
  • Journal Title: J Immunol 181(2) Pages: 1526-1535
  • Peer Reviewed
• [Journal Article] Genetic characterization of human Dsg3-specific B cells isolated by flow cytometry from the peripheral blood of patients with pemphigus vulgaris (2008)
  • Author(s): Yamagami J, Takahashi H, Ota T, Amagai M.
  • Journal Title: J Dermatol Sci 52 Pages: 98-107
  • NAID: 10024457486
  • Peer Reviewed
• [Journal Article] Novel system evaluating in vivo pathogenicity of desmoglein 3-reactive T cell clones using murine nemohieus vulgaris (2008)
  • Author(s): Takahashi H, Amagai M, Nishikawa T, Fuiii Y, Kawakami Y, Kuwana M
  • Journal Title: J Immunol 181 Pages: 1526-1535
  • Peer Reviewed
• [Presentation] デスモグレイン3反応性T細胞クローンは多クローンIgG型抗Dsg3抗体産生を誘導する (2008)
  • Author(s): 高橋勇人、桑名正隆、天谷雅行
  • Organizer: 第822回日本皮膚科学会東京地方会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-20
• [Presentation] デスモグレイン3反応性T細胞クローンは多クローンlgG型抗Dsg3抗体産生を謬導する (2008)
  • Author(s): 高橋勇人、桑名正隆、天谷雅行
  • Organizer: 第822回日本庫膚科学会東京地方会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-20
• [Presentation] 天疱瘡モデルマウスにおいて、デスモグレイン3反応性T細胞クローンは多クローンIgG型抗デスモグレイン3抗体産生を誘導する (2008)
  • Author(s): 高橋勇人、桑名正隆、天谷雅行
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] 天疱瘡モデルマウスにおいて、デスモグレイン3反応性T細胞クローンは多クローンlgG型抗デスモグレイン3抗体産生を誘導する (2008)
  • Author(s): 高橋勇人、桑名正隆、天谷雅行
  • Organizer: 第38回日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] Dsg3-reactive T cells ; a key player in the autoantibody production in pemphigus (2008)
  • Author(s): Hayato Takahashi、Masataka Kuwana、Masayuki Amagai
  • Organizer: International Meeting on Autoimmune Bullous Disease
  • Place of Presentation: Otsu, Japan
  • Year and Date: 2008-05-18
• [Presentation] Dsg3-reactive T cells ; a key player in the autoantibody production in pe mphigus (2008)
  • Author(s): Havato Takahashi, Masataka Kuwana, Masayuki Amagai
  • Organizer: International Meeting on Autoimmune Bullous Disease
  • Place of Presentation: 大津
  • Year and Date: 2008-05-18
• [Presentation] Single desmoglein 3-reactive CD4+ T cell clones activate polyclonal naive B cells and promote the production of pathogenic IgG in experimental pemphigus vulgaris (2008)
  • Author(s): Hayato Takahashi、Masataka Kuwana、Masayuki Amagai
  • Organizer: International Investigative Dermatology2008
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-05-17
• [Presentation] Single desmoglein 3-reactive CD4^+ T cell clones activate polyclonal naive B cells and promote the production of pathogenic IgG in experimental nemnhigus vulearis (2008)
  • Author(s): Havato Takahashi, Masataka Kuwana, Masayuki Amagai
  • Organizer: International Investigative Dermatology 2008
  • Place of Presentation: 京都
  • Year and Date: 2008-05-14
• [Presentation] 天疱瘡モデルマウスを用いた自己反応性T細胞株の仙丙9病原性評価法の確立 (2007)
  • Author(s): 高橋 勇人, 他3名
  • Organizer: 第816回東京支部研究地方会
  • Place of Presentation: 東京
  • Year and Date: 2007-12-15
• [Presentation] Interleukin-4 as a critical mediator derived from desmoglein 3-reactive T cells in the mouse pemphigus vulgaris model (2007)
  • Author(s): Hayato Takahashi、Masayuki Amagai、Takeji Nishikawa、Yutaka Kawakami、Masataka Kuwana
  • Organizer: The 37th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Tokyo
  • Year and Date: 2007-11-20
• [Presentation] A novel system for evaluation of in vivo pathogenicity of desmoglein 3-reactive T cell clones : a critical role of interleukin-4 in the mouse pemphigus vulgaris model (2007)
  • Author(s): Hayato Takahashi、Masayuki Amagai、Takeji Nishikawa、Yutaka Kawakami、Masataka Kuwana
  • Organizer: The Society for Investigative Dermatology 68th Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2007-05-12
• [Presentation] 天疱瘡モデルマウスを用いた自己反応性T細胞株のin vivo病原性評価法の確立 (2007)
  • Author(s): 高橋勇人、天谷雅行、西川武二、桑名正隆
  • Organizer: 第816回東京支部研究地方会
  • Place of Presentation: 東京
  • Year and Date: 2007-02-15
• [Presentation] Interleukin-4 as a critical mediator derived from desmoglein 3-reactive T cells in the mouse pemphigus vulgaris model (2007)
  • Author(s): Hayato Takahashi, et. a1.
  • Organizer: The 37th annual meeting of the Japanese Societyfor Immunology
  • Place of Presentation: Tokyo
• [Presentation] A novel system for evaluation of in vivo pathogenicity of desmoglein3-reactive T cell clones: a critical role of interleukin-4 in the mousepemphigus vulgaris model (2007)
  • Author(s): Hayato Takahashi, et. a1.
  • Organizer: The Society for Investigative Dermatology68th Annual Meeting
  • Place of Presentation: Philadelphia