Skin barrier abnormality in the pathogenesis of psoriasis

• Project/Area Number: 24591656
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kochi University
• Principal Investigator: NAKAJIMA Kimiko 高知大学, 教育研究部医療学系, 准教授 (20403892)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA Hideki 高知大学, 教育研究部医療学系, 講師 (70314995) ; SHIGA Takeo 高知大学, 教育研究部医療学系, 助教 (70444768) ; SANO Shigetoshi 高知大学, 教育研究部医療学系, 教授 (80273621)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 乾癬 / 皮膚バリア / セラミド / IL-17 / gd-T 細胞 / バリア障害 / 自然免疫 / IL-23/Th17軸

Outline of Final Research Achievements

Ceramides play an essential role in the epidermal permeability barrier. We generated Sptlc2 targeted mice under control of the keratin 5 promoter (SPT-cKO mice), thereby knocking out the function of serine palmitoyltransferase (SPT), the critical enzyme for ceramide biosynthesis. SPT-cKO mice impaired water-holding capacity and barrier function. From 2 weeks of age, they developed skin lesions like psoriasis. Skin lesions showed up-regulation of psoriasis-associated genes, such as IL-17A, IL-17F, IL-22. In the skin lesions and draining lymph nodes, there were increased numbers of γδ T cells that produced IL-17 (γδ－17 cells), most of which also produced IL-22. In vivo treatment of SPT-cKO mice with an anti-IL-12/23p40 antibody ameliorated the skin lesions and reduced the numbers of γδ-17 cells. Therefore, we conclude that a ceramide insufficiency in the epidermis leads to psoriasis-like lesions in mice, likely mediated by IL-23-dependent IL-22-producing γδ-17 cells.

Research Products

• [Journal Article] 表皮特異的セラミド合成酵素ノックアウトマウスはIL-23依存性IL-17産生gd-T細胞の増加と乾癬要病変を呈する (2014)
  • Author(s): 中島喜美子
  • Journal Title: 第28回角化症研究会記録集 Volume: 28 Pages: 121-125
  • Peer Reviewed
• [Journal Article] 脂漏性皮膚炎，接触性皮膚炎 (2014)
  • Author(s): 中島喜美子
  • Journal Title: medicina Volume: 51 Pages: 894-897
  • Peer Reviewed
• [Journal Article] Successful treatment of Schnitzler syndrome with cyclosporine. (2014)
  • Author(s): Nakajima K. Takahashi M, Yamamoto M, Takahashi A, Sano S, Kodama H, Arima K, Ida H.
  • Journal Title: Int J Dermatol. Volume: 53 Issue: 7
  • DOI: 10.1111/ijd.12300
  • Peer Reviewed / Open Access
• [Journal Article] Barrier abnormality due to ceramide deficiency leads to psoriasiform inflammation in a mouse model. (2013)
  • Author(s): Nakajima K, Terao M, Takaishi M, Kataoka S, Goto-Inoue N, Setou M, Horie K, Sakamoto F, Ito M, Azukizawa H, Kitaba S, Murota H, Itami S, Katayama I, Takeda J, Sano S.
  • Journal Title: J Invest Dermatol. Volume: 133 Issue: 11 Pages: 2555-2565
  • DOI: 10.1038/jid.2013.199
  • Peer Reviewed
• [Presentation] Cold-sensing ameliorated ichthyosis in a patient with Dorfman-Chanarin syndrome (2015)
  • Author(s): Tomoko Matsushima,Mayumi Ujihara,Mika Teraishi,Yoshikazu Uchida,Shigetoshi
  • Organizer: 73rd American Academy of Dermatology Annual Meeting 2015
  • Place of Presentation: The Moscone Center, San Francisco, CA(USA)
  • Year and Date: 2015-03-20 – 2015-03-24
• [Presentation] 基礎から見た乾癬～モデルマウスを用いた乾癬病態の検討～ (2014)
  • Author(s): 中島喜美子
  • Organizer: 第29回日本乾癬学会
  • Place of Presentation: 高知市文化プラザかるぽーと(高知市）
  • Year and Date: 2014-09-19 – 2014-09-20
• [Presentation] Langerin-expressing cells are despensable for development of psoriasis-like lesions in a mouse model (2014)
  • Author(s): Nakijima K, Kataoka S, M.Yamamoto, B.Malissen, M.Takaishi and S.Sano
  • Organizer: 11th Meeting of the German-Japanese Society of Dermatology (GJSD)
  • Place of Presentation: Marriott Hotel (Heidelberg, Germany)
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] 表皮特異的セラミド合成酵素ノックアウトマウスはIL-23依存性IL-17産生gd-T細胞の増加と乾癬様病変を呈する (2013)
  • Author(s): 中島喜美子
  • Organizer: 第28回角化症研究会
  • Place of Presentation: 東京商工会議所
• [Presentation] 表皮細胞からみた乾癬の病態 (2013)
  • Author(s): 中島喜美子
  • Organizer: 第28回日本乾癬学会学術大会
  • Place of Presentation: 東京ドームホテル
• [Presentation] Ceramide deficiency in epidermis leads to the development of psoriasis-like lesions associated with IL-23-dependent proliferation of gd-17 cells (2012)
  • Author(s): Nakajima K, Kataoka S, Inoue N, Terao M, Murota H, Azukizawa H, Setou M, Katayama I, Takeda J, Sano S
  • Organizer: 99th Annual Meeting: The American Association of Immunologists
  • Place of Presentation: Hynes Contention Center（米国）
• [Presentation] Ceramide deficiency in epidermis leads to the development of psoriasis-like lesions associated with IL-23-dependent proliferation of gd-17 cells (2012)
  • Author(s): Nakajima K, Kataoka S, Inoue N, Terao M, Murota H, Azukizawa H, Setou M, Katayama I, Takeda J, Sano S
  • Organizer: 75th Annual Meeting: Society for Investigative Dermatology
  • Place of Presentation: Raleigh Convention Center（米国）
• [Presentation] 表皮脂質異常と皮膚バリア障害 (2012)
  • Author(s): 中島喜美子
  • Organizer: 第111回日本皮膚科学会総会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 表皮細胞特異的セラミドノックアウトマウスはIL-23依存性γδ-IL-17細胞増加と乾癬様病変を呈する (2012)
  • Author(s): 中島喜美子、片岡佐誉、寺尾美香、小豆澤宏明、片山一朗、竹田潤二、佐野栄紀
  • Organizer: 第27回日本乾癬学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟）
• [Presentation] Ceramide deficiency in the epidermis leads to development of psoriasis-like lesions associated with IL-23-dependent proliferation of gd-17 cells (2012)
  • Author(s): 中島喜美子、片岡佐誉、寺尾美香、片山一朗、竹田潤二、佐野栄紀
  • Organizer: 第40回日本臨床免疫学会総会
  • Place of Presentation: 京王プラザホテル（東京）
• [Book] 第28回角化症研究会記録集 (2014)
  • Author(s): 中島喜美子
  • Total Pages: 147
  • Publisher: 株式会社 協和企画