Identification of pathogenic antigen-presenting cells and therapeutic targets in inflammatory skin diseases.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16211
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyoto University
• Principal Investigator: Nakamizo Satoshi 京都大学, 医学研究科, 特定講師 (30769740)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アトピー性皮膚炎 / 尋常性乾癬 / 樹状細胞 / マクロファージ / 1細胞RNAシークエンス

Outline of Final Research Achievements

Flow cytometry analysis combined with one-cell RNA sequencing analysis was used to classify human cutaneous dendritic cells into four populations, DC1, DC2, DC3 and activated DC, and macrophages into three populations, CCR1-positive, MARCO-positive and TREM2-positive macrophages. Activated DCs were increased in both atopic dermatitis and psoriasis and produced IL-15, which is important for dermatitis; DC3 were increased only in psoriasis and produced IL-1B and IL-23A, which are essential for the development of psoriasis; TREM2-positive DCs were increased in psoriasis and produced IL-15, which is important for psoriasis; TREM3-positive DCs were increased in atopic dermatitis and produced IL-15, which is important for psoriasis. These results suggest that newly identified activated DCs and DC3 may play a pivotal role in inflammatory skin diseases.

Free Research Field

皮膚免疫学

Academic Significance and Societal Importance of the Research Achievements

学術的な意義として、1.細胞RNAシークエンス解析とフローサイトメトリー解析を組み合わせ、皮膚の抗原提示細胞分画を詳細に解析したこと、2.新たに同定された活性化DCとDC3が皮膚炎症に重要な役割を担っている可能性を示したことが挙げられる。これらの知見は、皮膚免疫システムの理解を大きく進展させ、炎症性皮膚疾患の病態解明につながる可能性がある。
社会的な意義としては、この研究成果が新規治療薬開発につながる可能性が考えられる。また、皮膚の免疫システムの理解を深めることで、皮膚がんや感染症などの皮膚疾患への応用も期待できる。