2010 Fiscal Year Final Research Report
Mechanism of nucleic acid recognition by endosomal Toll-like receptor 3
| Project/Area Number |
20590483
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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 | Hokkaido University |
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Principal Investigator |
MATSUMOTO Misako Hokkaido University, 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) |
2008 – 2010
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| Keywords | 樹状細胞 / Toll-like receptor / 二重鎖RNA / タイプIインターフェロン / ウイルス感染 / エンドソーム / エンドサイトーシス / プロテオーム |
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| Research Abstract |
The synthetic virus double-stranded RNA analogue, poly (I:C), extracellularly activates both the endosomal Toll-like receptor (TLR) 3 and the cytoplasmic RNA helicase, melanoma differentiation-associated gene 5, leading to the production of type I interferons (IFNs) and inflammatory cytokines, and dendritic cell (DC) maturation. The mechanism by which extracellular poly(I:C) is delivered to TLR3-positive organelles and the cytoplasm remains to be elucidated. In this study, we demonstrate that the cytoplasmic lipid raft protein, Raftlin, is essential for poly (I:C) cellular uptake in human myeloid DCs and epithelial cells. When Raftlin was silenced, poly (I:C) failed to enter cells and induction of IFN-β production was inhibited. Upon poly (I:C) stimulation, Raftlin was translocated from the cytoplasm to the plasma membrane where it colocalized with poly (I:C), and thereafter moved to TLR3-positive endosomes. Raftlin physically associated with clathrin at the plasma membrane in response to poly (I:C). Thus, Raftlin cooperates with the clathrin-AP-2 complex to mediate cell entry of poly (I:C), which is critical for activation of TLR3.
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[Journal Article] Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3.2009
Author(s)
Iwakiri, D., L.Zhou, M Samanta, M.Matsumoto, T.Ebihara, T.Seya, S.Imai, M.Fujieda, K.Kawa, K.Takada
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Journal Title
J.Exp.Med. 206
Pages: 2091-2099
Peer Reviewed
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[Journal Article] Increased expression of Toll-like receptor 3 in intrahepatic bilinary epithelial cells at sites of ductular reaction in diseased livers.2008
Author(s)
Nakamura, M., K.Funami, A.Komori, T.Yokoyama, Y.Aiba, A.Araki, Y.Takii, M.Ito, M.Matsuyama, H.Yatsuhashi, M.Matsumoto, H.Ishibashi, T.Seya
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Journal Title
Hepatol.Int. 2
Pages: 222-230
Peer Reviewed
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