2023 Fiscal Year Final Research Report
Development of new treatment for psoriasis targeting CD147/basigin
Project/Area Number |
21K08329
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53050:Dermatology-related
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Research Institution | Kagoshima University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
古川 龍彦 鹿児島大学, 医歯学域医学系, 教授 (40219100)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | CD147/Basigin / 乾癬 / T細胞分化 / Th17細胞 / モノカルボン酸トランスポータ |
Outline of Final Research Achievements |
We demonstrated that CD147/basigin regulates cancer cell proliferation and invasion through the glycolytic pathway. Recent studies showed that differentiation and activation of T lymphocytes also depend on glycolysis for energy. We revealed that CD147 is involved in the development of psoriasis, an immunological disease caused by abnormal differentiation and proliferation of T cells. CD147 promotes the differentiation of naive T cells into Th17 cells which play the pivotal role in psoriasis. The development of experimental psoriasis was suppressed in the mice deficient in CD147 gene. Based on these findings, we planned this research with the aim of developing a new treatment for psoriasis that inhibits glycolysis targeting CD147. In silico virtual screening resulted in a list of 183 candidate compounds. Among these compounds, we identified several compounds that inhibit the differentiation of CD4+ T cells into Th17 cells through suppression of glycolysis and are not cytotoxic.
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Free Research Field |
皮膚科学
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Academic Significance and Societal Importance of the Research Achievements |
乾癬はCD4+ T細胞が種々の因子の刺激によりTh17細胞へ分化しIL-17の産生が亢進することにより発症する。近年使用される生物学的製剤はサイトカインを標的とし、JAK阻害薬やPDE4阻害薬はサイトカイン産生を抑制する。CD147/basiginを標的とする治療はCD4+ T細胞のサイトカイン産生細胞への分化を抑制することを目的としており、従来の治療とは全く異なるより根本的な治療である。乾癬の治療は日進月歩の観を呈している。しかし本症は難治性皮膚疾患であり未だに完治しない症例が少なくない。この研究成果は新たな治療法の開発に結び付く可能性が高く社会的意義を有する。
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