| Project/Area Number |
17390140
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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 |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
IWAKURA Yoichiro The University of Tokyo, The Institute of Medical Science, Professor (10089120)
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| Co-Investigator(Kenkyū-buntansha) |
SAIJO Shinobu The Institute of Medical Science, 医科学研究所, Assistant Professor (60396877)
KAKUTA Shigeru The Institute of Medical Science, 医科学研究所, Assistant Professor (80345032)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,550,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Animal disease models / cvtokine / Rheumatiod arthritis / Inflmmation / Dendritic Cells / C-type lectin / Autoimmune / Innate immunity / マウス / 発生工学 / 自己免疫疾患 / マイクロアレイ / ノックアウトマウス / トランスジェニックマウス |
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| Research Abstract |
Dendritic cells are one of the most powerful antigen presenting cells. To analyze the roles of dendritic cells int development of arthritis, we used two C-type lectin KO mice, Dectin-1 KO mice and DCIR KO mice. These genes were up-regulated in the joints of HTLV-I Tg mice nad IL-1Ra KO mice. In vivo, b-glucan induced cytokine production from wild-type mice and macrophages was abolished in Dectin-1 KO mice. In vivo, Dectin-1 mice was susceptible against fungal infection. On the other hand, we found that aged DCIR KO mice spontaneously develop sialadenitis and enthesitis associated with elevated serum autoantibodies. DCIR KO mice showed markedly exacerbated response to collagen-induced arthritis. The DC population was expanded excessively in aged and type II collegen-immunized DCIR KO mice. Upon treatment with granulocyte-macrophage colony-stimulating factor, DCIR KO mice^derived bone marrow cells (BMCs) differentiated into DCs more efficiently than did wild-type BMCs, owing to enhanced signal transducer and activator of transcription-5 phosphorylation. These observation indicate that DCIR is a negative regulator of DC expansion and has a crucial role in maintaining the homeostasis of the immune system.
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