Skin barrier abnormality in the pathogenesis of psoriasis

2014 Fiscal Year Final Research Report

• 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
• Keywords: 乾癬 / 皮膚バリア / セラミド / IL-17 / gd-T 細胞

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.

Free Research Field

皮膚免疫