| Project/Area Number |
21200079
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
Infectious disease medicine
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| Research Institution | Hokkaido University |
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Principal Investigator |
MATSUMOTO Misako 北海道大学, 大学院・医学研究科, 准教授 (30332456)
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| Co-Investigator(Renkei-kenkyūsha) |
SEYA Tsukasa 北海道大学, 大学院・医学研究科, 教授 (10301805)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥30,940,000 (Direct Cost: ¥23,800,000、Indirect Cost: ¥7,140,000)
Fiscal Year 2011: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2010: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2009: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
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| Keywords | 自然免疫 / Toll-like receptor / ウイルス感染 / 樹状細胞 / タイプIインターフェロン / 炎症性サイトカイン / エンドサイトーシス / プロテオーム / 炎症応答 / インターフェロン / 二次構造予測 / 細胞外核酸 / クラスリン / エンドソーム / アダプター分子 |
|---|
| Research Abstract |
Toll-like receptor (TLR) 3 recognizes dsRNA in the endosomes and induces type I interferon and proinflammatory cytokine production, and dendritic cell (DC) maturation via the adaptor protein TICAM-1. The mechanism by which extracellular dsRNA is delivered to TLR3-positive organelles remains to be elucidated. In this study, we demonstrate that TLR3 recognizes virus-derived ssRNAs with stable stem structures, in addition to dsRNA, and that the cytoplasmic lipid raft protein, Raftlin, is essential for dsRNA/ssRNA cellular uptake in human myeloid DCs and epithelial cells. Raftlin physically associates with clathrin at the plasma membrane in response to dsRNA and mediates cell entry of dsRNA/ssRNA, which is critical for activation of TLR3. Hence, both cell-surface and endosomal recognition of RNAs by the uptake receptor and TLR3, respectively, is required for TLR3 activation.
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