Molecular mechanism of skin inflammation induced by desmoglein 3-specific T cells

• Project/Area Number: 26293258
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: Takahashi Hayato 慶應義塾大学, 医学部, 講師 (40398615)
• Co-Investigator(Kenkyū-buntansha): 佐々木 貴史 慶應義塾大学, 医学部, 講師 (70306843) ; 天谷 雅行 慶應義塾大学, 医学部, 教授 (90212563)
• Research Collaborator: O'Shea John National Institutes of Health, National Institute of Musculoskeletal and Skin Diseases
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: Interface dermatitis / Desmoglein / T cell / デスモグレイン / コレステロール25-水酸化酵素 / 皮膚免疫 / 免疫学

Outline of Final Research Achievements

Interface dermatitis is a pathological feature which is commonly observed in a variety of skin diseases including lichen plans, severe drug adverse reaction, graft-versus-host disease, paraneoplastic pemphigus and so on. The molecular mechanism that leads to interface dermatitis has not been understood. In this project, we took advantage of genetically engineered mice and discovered that T-bet and Stat1, crucial transcriptional factors in T cell differentiation, are keys in development of interface dermatitis. On the other hand, we also sought to establish a novel concept in the field of Immunology in this project. Through investigating genes which are specifically induced by interleukin (IL)-27, we found that cholesterol metabolizing enzyme is induced by IL-27 and the function contributes to immune regulation. Our results are promisingly expected to be useful to invent a new treatment for skin inflammatory diseases in the future.

Research Products

• [Journal Article] Pemphigus (2017)
  • Author(s): Michael Kasperkiewicz, Christoph T. Ellebrecht, Hayato Takahashi, Jun Yamagami, Detlef Zillikens, Aimee S. Payne and Masayuki Amagai
  • Journal Title: Nature Reviews Disease Primers Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Novel immune regulation by CD4+ T cells via cholesterol 25-hydroxylase pathway. (2017)
  • Author(s): Hayato Takahashi, Hisashi Nomura, Hisato Iriki, Akiko Kubo, Yohei Mikami, Yuka Kanno, John O’Shea, Masayuki Amagai
  • Organizer: 第24回分子皮膚科学フォーラム
  • Place of Presentation: ベルサール東京日本橋（東京都中央区）
  • Year and Date: 2017-04-14
• [Presentation] 25-hydroxycholesterol secreted from CD4+ T cells mediates novel immune regulation by interleukin-27 (2016)
  • Author(s): Hayato Takahashi, Hisashi Nomura, Hisato Iriki, Yohei Mikami, Yuka Kanno, John O’Shea, Masayuki Amagai
  • Organizer: The 45th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Novel immune regulation by CD4+ T cells via cholesterol 25-hydroxylase pathway. (2016)
  • Author(s): Hayato Takahashi, Hisashi Nomura, Hisato Iriki, Akiko Kubo, Yohei Mikami, Yuka Kanno, John O’Shea, Masayuki Amagai
  • Organizer: European Society for Dermatological Research Annual Meeting 2016
  • Place of Presentation: ミュンヘン（ドイツ）
  • Year and Date: 2016-09-07
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] ２５－ヒドロキシコレステロールを有効成分として含有してなる、活性化されたＴ細胞及び／又はＢ細胞に選択的な細胞死誘導剤又は細胞死促進剤 (2016)
  • Inventor(s): 高橋勇人、天谷雅行
  • Industrial Property Rights Holder: 高橋勇人、天谷雅行
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-111556
  • Filing Date: 2016-06-03