| Project/Area Number |
15H04879
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Juntendo University |
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Principal Investigator |
OHNUMA Kei 順天堂大学, 医学(系)研究科(研究院), 准教授 (10396872)
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| Co-Investigator(Kenkyū-buntansha) |
森本 幾夫 順天堂大学, 医学(系)研究科(研究院), 特任教授 (30119028)
岩尾 憲明 順天堂大学, 医学部, 准教授 (00309139)
岩田 哲史 順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (00396871)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 慢性GVHD / CD26 / Caveolin-1 / IL-26 / 造血幹細胞移植 / GVHD / caveolin-1 / 線維化 / DPP4 / 移植免疫学 / 小児血液学 |
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| Outline of Final Research Achievements |
Obliterative bronchiolitis (OB) is the only manifestation of pulmonary chronic GVHD (cGVHD). We identified a novel effect of IL-26 on cGVHD. Humanized cGVHD mice exhibited OB with increased collagen deposition and predominant infiltration with human IL-26CD26CD4T cells. IL-26 increased collagen synthesis in fibroblasts and that collagen contents were increased in a murine GVHD model using IL26 Tg mice. IA significant increase in IL-26 production by CD4T cells following CD26 costimulation, while immunoglobulin Fc domain fused with the N-terminal of caveolin-1, the ligand for CD26, (Cav-Ig) effectively inhibited production of IL-26. Administration of Cav-Ig before or after onset of GVHD impeded the development of cGVHD without interrupting engraftment of donor-derived human cells, with preservation of the GVL effect. We concluded that cGVHD of the lungs is caused in part by IL-26CD26CD4T cells, and that treatment with Cav-Ig could be beneficial for cGVHD prevention and therapy.
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