Comprehensive studies on the contribution of CD147/basigin to Th cell differentiation and pathogenesis of psoriasis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kagoshima University
• Principal Investigator: Kanekura Takuro 鹿児島大学, 医歯学域医学系, 教授 (70177509)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: CD147/Basigin / 乾癬 / 解糖系 / Th17細胞 / MCT

Outline of Final Research Achievements

Th17 plays an important role in psoriasis. The differentiation of naive CD4+ T-cells into Th17 cells depends on glycolysis as an energy source. CD147/Basigin regulates glycolysis in association with monocarboxylate transporters (MCT)-1 and - 4 in cancer- and T-cells. We examined whether CD147/Basigin is involved in the pathogenesis of psoriasis using samples from humans and psoriasis-model mice. The serum level of CD147 was increased in psoriasis patients and the expression of CD147 and MCT-1 was elevated on their dermal CD4+ RORγt+ T cells. In vitro, the potential of naive CD4+ T cells to differentiate into Th17 cells was abrogated in CD147-/- T-cells. Imiquimod (IMQ)-induced psoriatic dermatitis was significantly milder in CD147-/- mice and bone marrow chimeric mice lacking CD147 in hematopoietic cells of myeloid lineage. These findings demonstrate that CD147 is essential for the development of psoriasis via the induction of Th17 cell differentiation.

Free Research Field

難治性皮膚疾患、特に好中球性皮膚疾患と強皮症の病態に関する分子細胞生物学的研究と治療法の開発．

Academic Significance and Societal Importance of the Research Achievements

CD147/basiginは申請者ら自身がクローニングした分子であり、CD147/basiginとT細胞の分化機構の観点から乾癬の病態を包括的に解明したもので学術的に極めて先駆的かつ独創的なものである。近年乾癬治療に用いられる生物学的製剤はTh17細胞が産生するIL-17やTh17を活性化するIL-23をターゲットとしているのに対して、Th17細胞への分化を制御するより根本的な治療の開発につながる成果であり社会的意義が大きい。またTh17細胞関連疾患には乾癬以外にも多くの疾患が含まれるので本研究の意義は皮膚科領域にとどまらず学際的で重要性の高いものである。