| Project/Area Number |
24591656
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kochi University |
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Principal Investigator |
NAKAJIMA Kimiko 高知大学, 教育研究部医療学系, 准教授 (20403892)
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| 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)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥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)
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| 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 |
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| 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.
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