2020 Fiscal Year Final Research Report
Roles for CD157 in functions of macrophage lineage cells and early pathophysiology of a rheumatoid arthritis model
| Project/Area Number |
17K08798
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
矢作 綾野 川崎医科大学, 医学部, 助教 (10584873)
井関 將典 川崎医科大学, 医学部, 講師 (30532353)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | 結核 / 単球・マクロファージ / Toll様受容体2 / 活性酸素 / 関節リウマチ / IL-6/gp130/STAT3 / 滑膜細胞 / 線維化 |
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| Outline of Final Research Achievements |
Collaboration study with Dr. Chen, who discovered increases of BST-1/CD157 in the sera and lung granuloma of the patients with tuberculosis, revealed increased susceptibility to Mycobacterium (M.) tuberculosis in Bst1-knockout mice(Bst1KO), and impaired signal transduction from TLR2/PKC zeta to production of reactive oxygen spices by macrophages lacking BST-1. In the early phase of arthritis in gp130F759, a murine model for rheumatoid arthritis, CX3CR1+ macrophage-like synoviocytes increased in the synovium and a CX3CR1+ monocyte subset decreased in the peripheral blood, indicating that local inflammation is reflected in the changes of subsets in peripheral blood. Lack of BST-1 ameliorated fibrosis in the synovium of gp130F759. We clarified physiological roles for BST-1 on macrophages in defense against M. tuberculosis and pathological roles of BST-1 promoting fibrosis in arthritis like rheumatoid arthritis.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
BST-1(Bone marrow stromal cell antigen-1)/ CD157は関節リウマチ由来骨髄間質細胞に高発現するGPIアンカー型細胞膜外酵素(ADPリボシルシクラーゼ)であり、腸管-神経-免疫系の機能を制御する多機能分子である。ヒトとマウスで共通してBST-1を表面発現する細胞である単球・マクロファージ系に注目して、生体レベルでBST-1の機能解析を進めた結果、世界的に重要な感染症である結核に対する感染抵抗性促進機能、頻度の高い自己免疫疾患である関節リウマチのマウスモデルにおける線維化促進機能を明らかにしたことは、両疾患の治療法開発に有用な基盤的知見を提供する。
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