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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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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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 / preclinical phase / 滑膜炎 / マクロファージ / 末梢血単球亜集団 / IL-6/gp130 / 血管新生 / 可溶性BST-1 / ROS産生 / TLR2 / Bst1-flox / gp130 / 骨髄系細胞特異的BST-1欠損 / BST-1 / CD157 / gp130F759 / マクロファージ様滑膜細胞 / 単球・マクロファージ亜集団 / CX3CR1 / CD157レポーターマウス / ADPリボシルシクラーゼ / BST-1/CD157 / CD38 / 関節リウマチモデル / 滑膜 |
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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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| 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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Report
(5 results)
Research Products
(29 results)
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[Journal Article] Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages.2020
Author(s)
Covarrubias AJ, Kale A, Perrone R, Lopez-Dominguez JA, Pisco AO, Kasler HG, Schmidt MS, Heckenbach I, Kwok R, Wiley CD, Wong HS, Gibbs E, Iyer SS, Basisty N, Wu Q, Kim IJ, Silva E, Vitangcol K, Shin KO, Lee YM, Riley R, Ben-Sahra I, Ott M, Ishihara K, Quake SR, Newman J, Brenner C, Campisi J, Verdin E. et al
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Journal Title
Nat Metab
Volume: 2
Issue: 11
Pages: 1265-1283
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CD157 Marks Tissue-Resident Endothelial Stem Cells with Homeostatic and Regenerative Properties.2018
Author(s)
Wakabayashi T, Naito H, Suehiro JI, Lin Y, Kawaji H, Iba T, Kouno T, Ishikawa-Kato S, Furuno M, Takara K, Muramatsu F, Weizhen J, Kidoya H, Ishihara K, Hayashizaki Y, Nishida K, Yoder MC, Takakura N.
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Journal Title
Cell Stem Cell.
Volume: 22
Issue: 3
Pages: 348-397
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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