| Project/Area Number |
18590990
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kobe University |
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Principal Investigator |
YASUDA Hisafumi Kobe University, Graduate School of Medicine, Clinical Researcher (50403233)
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| Co-Investigator(Kenkyū-buntansha) |
YOKONO Koichi Kobe University, Graduate School of Medicine, Professor (50144580)
NAGATA Masao Kobe University, Graduate School of Medicine, Associate Professor (70294220)
HARA Kenta Kobe University, Graduate School of Medicine, Assistant Professor (70397826)
MORIYAMA Hiroaki Kobe University, Graduate School of Medicine, Clinical Researcher (70372646)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | type 1 diabetes / autoimmunity / bone marrow cell / CD11c / regulatory dendritic cell / cytokine / regulatory T cell / immune tolerance |
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| Research Abstract |
Generation of regulatory bone marrow-derived dendritic cells (BMDCs) cultured with immunoregulatory cytokine
Dendritic cell (DC) is one of the most important disease-regulators in the pathogenesis of type 1 diabetes (T1D). Our attempt to establish DC therapy to prevent diabetes in mouse model will increase our knowledge of pathogenesis and prevention of human T1D. To explore the immunoregulatory effect on autoimmune diabetes in NOD mice, bone marrow-derived DCs (BMDCs) were generated after 6 days' culture of NOD BM cells with GM-CSF and IL-10 or TGF-β1, designated G/10-DCs or G/T-DCs, respectively. To establish DC therapy to prevent autoimmune diabetes, various conditioned DCs have also been examined.
Prevention of T1D by transfer of regulatory BMDCs
G/10-DCs and G/T-DCs showed a higher uptake of FITC-dextran than G/4-DCs, indicating a higher capacity of endocytosis than G/4-DCs. In allo MLR, weaker T cell responses were seen in the presence of G/10-DCs or G/T-DCs than G/4-DCs, resulting
… More
in lower levels of IFN-γ production.
G/10-DCs were administered i.p. into female NOD mice three times at weekly intervals beginning at 2 weeks of age, resulting in significant prevention of diabetes onset at 35 wk (diabetes incidence; 10%), as compared with control mice treated with (90%) or without PBS (80%). Splenic T cells from G/10-DC-treated NOD mouse had a suppressor activity to delay diabetes-transfer into NOD-scid mice.
G/T-DCs were administered i.p. into female NOD mice as well, leading to complete prevention of diabetes at 35 wk (0/13). G/T-DCs secrete higher levels of IL-10 than G/4-DC. G/T-DC-treatment increased the ratio of DCs in treated mouse. Splenic T cells from tolerized mouse had a suppressor activity to delay diabetes-transfer into NOD-scid mice.
These results suggest that modulation of DCs with IL-10 or TGF-β1 may lead to the development of a useful therapeutic intervention for T1D. We also concluded that the modulation of DCs with TGF-β1 is the most suitable condition for the prevention of T1D. Less
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