Functional analysis of the non-HLA genes within major histocompatibility complex (MHC) region with the use of gene-targeted mice
| Project/Area Number |
13670320
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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 | University of Tokushima |
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Principal Investigator |
MATSUMITO Mitsuru Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (60221595)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHIMA Akemi Institute for Enzyme Research, Lecturer, 分子酵素学研究センター, 教務員 (70116862)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Lymphotoxin receptor / Signal transduction / NF-Kb / NIK / T cell / リンホトキシン / TNFレセプター / ノックアウトマウス |
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| Research Abstract |
NF-Kb-inducting kinase (NIK) is involved in lymphoid organogenesis in mice through lymphotoxin-b receptor signaling. To clarify the roles of NIK in T cell activation through TCR/CD3 and co atimulation pahways, we have studied the function of T cells from aly mice, a strain with mutant NIK. NIK mutant T cells showed impaired proliferation and IL-2 production in respones to anti-CD3 stim ulation, and these effects were caused by impaired NF-Kb activity in both mature and immature T cells; the impaired NF-Kb. In contrast, responses to co- stimulatory signals were largely retained in aly mice, suggesting that NIK is not uniquely coupled to the co-stim ulatory pathways. When NIK mutant T cells were stimulated in the presence of a protein kinase C (PKC) inhibitor, proliferative responses were abrogated more severely than in control mice, suggesting that both NIK and PKC control T cell activation in a cooperative manner. We also demonstrated that NIK and PKC are involved in distinct NF-Kb activation pathways downstream of TCR/CD3. These results suggest critical roles for NIK in setting the threshold for T cell activation, and partly account for the immunodeficiency in aly mice.
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Report
(3 results)
Research Products
(6 results)
