| Project/Area Number |
18590484
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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 |
Immunology
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
OGASAWARA Kouetsu Research Institute, International Medical Center of Japan, The Research Institute Department of Intractable Diseases, Division of Clinical Immunnology, Head (30323603)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Naruyoshi The Research Institute, International Medical Center of Japan, Department of Intractable Diseases, Division of Clinical Immunnology, Fellow (50365425)
TANAKA Kazusa (ISHIZAKI, Kazusa) The Research Institute, International Medical Center of Japan, Department of Intractable Diseases, Division of Clinical Immunnology, Fellow
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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 |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | autoimmunity / NKG2D / Diabetes / NODマウス / RAE-1 / NK細胞 / 転写制御 |
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| Research Abstract |
Autoimmune diseases are caused by abnormal immune responses in self-tissues. Co-stimulatory molecules play important roles in immune responses. We focused the signaling mechanisms of co-stimulatory molecules and their ligands to explore development of autoimmune diseases. Type I diabetes is an autoimmune disease in which insulin-producing beta cells in pancreatic islets are destroyed by auto-reactive T cells. We showed that autoreactive T cells infiltrating the pancreas in diabetic NOD mice express NKG2D and NKG2D ligands are present in the pre-diabetic pancreas islets. Treatment with anti-NKG2D monoclonal antibody during the pre-diabetic stage completely prevented disease by impairing expansion of autoreactive T cells and blocking their effector functions. However, the molecular mechanisms by which RAE-1, one of NKG2D ligands are expressed in the pancreas in the development diabetes are unknown. We found that RAE-1 expression is regulated by transcriptional factors and that RAE-1 alpha is a major NKG2D ligand in NOD. In addition, transcriptional activator (s) derived from NOD may regulate RAE-1 alpha expression.
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