Pathogenesis of virus induced diabetes
| Project/Area Number |
17390265
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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 |
Metabolomics
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NAGAFUCHI Seiho Kyushu University, School of Medicine, Professor, 医学部, 教授 (00150441)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Kazuya Kyushu University, Hospital, Research Associate (90311844)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2005: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | virus / diabetes / pancreatic islet / macrophages / apoptosis / 免疫学 / 細胞・組織 / シグナル伝達 / tyk-2 |
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| Research Abstract |
In order to clarify the pathogenesis of virus induced diabetes, we studied the relative importance of T cells, B cells, macrophages and antibody. Neutralizing antibody was effective in preventing the development of diabetes only when transferred within 36 hrs after infection. T cells nor B cells were not necessary to provide protection, because T cell deficient athymic nude mice, B cell deficient muMT.muMT mice, nor both T cell and B cell deficient Rag-1 knockout mice did not increase the induction of virus induced diabetes. In contrast, macrophage activation following immunopotentiator corynebacterium parvum significantly prevented mice from developing diabetes after challenge with diabetogenic EMC-D virus.
These data indicated that early protectivemechanims, as innate immunity but not acquired immunity, may be essential against virus induced diabetes. We further studied the interferon receptor signaling pathway. We found that Tyk-2 deficient mice were susceptible to the EMC-D virus in
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duced diabetes, accompanied by the increased virus growth, decreased insulin content of the pancreas. Serum interferon levels increased and treatment of interferon of Tyk-2 deficient cells inhibited the proliferation of the virus in vitro lower than that of normal cells.
We also studied the apoptosis associated molecule Siva, to examine whether the molecule may determine the susceptibility of the mice to the virus induced diabetes. Surprisingly, diabetes susceptible SJL mice possessed Siva mutation. However, intercross studies indicated that this mutation did not directly associated with the susceptibility. We developed RIP-Cre mouse and Bcl-x foxed mouse. The mated mice deficient in beta cell specific Bcl-x knockout mice did not increased the susceptibility to the EMC-D virus induced diabetes, indicating that other anti-apoptotic signals may play more important role in the protection against virus induced beta cell damage.
Further studies are required to delineate the pathogenesis of virus induced diabetes, which may be controlled by multiple factors including immunoprotective mechanisms and anti-apoptotic signals. Less
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Report
(3 results)
Research Products
(7 results)
