| Project/Area Number |
15390386
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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 |
General surgery
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| Research Institution | Fukuoka University |
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Principal Investigator |
YASUNAMI Yohichi Fukuoka University, School of Medicine, Associate Prof, 医学部, 助教授 (00166521)
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| Co-Investigator(Kenkyū-buntansha) |
RYU Shinichiro Fukuoka University, School of Medicine, Assistant Prof, 医学部, 助手 (30279286)
NAKANO Masahiko Fukuoka University, School of Medicine, Assistant Prof, 医学部, 助手 (90389354)
HABE Shigehisa Fukuoka University, School of Medicine, Lecturer, 医学部, 講師 (70037430)
永井 哲 福岡大学, 医学部, 助手 (10320300)
中山 俊憲 千葉大学, 大学院・医学研究院, 教授 (50237468)
勝田 仁 九州大学, 医学部, 助手 (50333240)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | islets / diabetes / rejection / engraftments / 移植膵島障害 / NKT細胞 / グラフト障害 |
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| Research Abstract |
Pancreatic islet transplantation has now become a procedure of choice for the treatment of insulin-dependent diabetes mellitus. Currently, however, the inability of achieving successful islet transplantation from one donor to one recipient is a major limiting factor, in which 2-3 cadaveric donor pancreases are required to cure a single recipient. Therefore, it is of quite significance to find a novel procedure to overcome the obstacle. In the present study, we focus on engraftments of islets into the liver, which is the site of clinical islet transplantation, facilitating to find a new way to minimize the number of donor islets required for successful transplantation.
Vα14 NKT cells belong to a distinct subset of lymphocytes bridging the innate and acquired immune systems and play an important role in the immediate responses, because Vα14 NKT cells produce large amounts of IFN-γ immediately after activation. Since Vα14 NKT cells are relatively abundant in the liver, the site of choice for islet transplantation, and since IFN-γ is believed to be an important factor in the destruction of islet βcells, we hypothesized that Vα14 NKT cells in the liver might be involved in islet graft failure. We find that natural killer T(NKT)cells play an essential role in islet graft failure in mice and that a molecule responsible for the effect by NKT cells is INF-γ. The depletion of INF-γ releas from NKT cells of a recipient with α-galactosylceramide, a synthetic ligand of NKT cells, prior to islet transplantation produced successful transplantation with islets from a single donor pancreas. Thus, the present study elucidates a novel role of NKT cells in engraftments of islets and provides a potential that islet transplantation from one donor to one recipient, even to more than one, becomes feasible by targeting at NKT cells.
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