2022 Fiscal Year Final Research Report
Elucidation of epithelial-dendritic cell network mechanism in oral lichen planus focusing on Cathepsin K
| Project/Area Number |
19K19165
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 口腔扁平苔癬 / カテプシンK / TLR9 / Th17 / 樹状細胞 |
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| Outline of Final Research Achievements |
pDCs were extracted from human PBMCs, stimulated with (1) (pDC only), (2) (pDC + TLR9 agonist), (3) ((2) + CTSK), and (4) ((3) + CTSK inhibitor) and cultured. Comparing the amount of Th17-related cytokine production, their expression was predominantly enhanced in (3).
When immune cells were extracted from OLP tissue by CD45 and RNA-seq was performed, TLR9 was strongly expressed in pDC. Pathway analysis revealed that the TLR9+ pDCs had elevated Th17 differentiation pathways and T cell activation pathways.
These results suggest that CTSK promotes TLR9-mediated production of Th17-related cytokines in pDCs, activates Th17 differentiation, and promotes pathogenesis of OLP.
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| Free Research Field |
口腔外科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、口腔扁平苔癬( OLP)の病態形成における上皮-樹状細胞ネットワーク機構を解明することで、最終的には新規標的分子治療の確立を目指すものである。
臨床的には OLP は局所へのステロイド塗布が第一選択薬であるが、ステロイドに対し抵抗性を持つ症例や再発する症例も少なくない。そのため、OLP の発症・病態進展の抑制が重要であり、ステロイドに代わる新たな治療が望まれている。本研究で期待できる成果は、 OLP 病変局所の粘膜上皮や間質がそれぞれ特異的に発現している新規関連分子を解析することで、それらを標的とする新規標分子治療へ展開できる可能性があり、極めて有意義な研究である。
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