The regulation of cytokine production by phospholipid on MVB
| Project/Area Number |
26860189
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
Sasai Miwa 大阪大学, 微生物病研究所, 助教 (30631551)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | TLR / IFN / trafficking / サイトカイン産生 / 感染制御 / 小胞輸送 |
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| Outline of Final Research Achievements |
Recent studies indicate that signals from these TLRs bifurcate at the level of distinct endosomal compartments to mediate the induction of cytokine and type I interferon (IFN) genes. TLR9 mediates signals for cytokines from VAMP3+ endosome, and induces IFN genes from LAMP2+ endosome. Phosphoinositides mark distinct subcellular membranes and control membrane trafficking. However, their role in TLR trafficking and signaling remains unclear. Here, we examined the role of phosphatidylinositol 3P 5-kinase, PIKfyve, in TLR trafficking and signaling. We demonstrate that inhibition of PIKfyve activity preferentially blocks TLR9 signaling for type I IFN induction in pDCs. By confocal microscopy, we show that trafficking of both TLR9 and CpG to the LAMP1+ compartment is blocked by PIKfyve inhibitor treatment. These data indicate that PIKfyve provides critical phosphoinositides necessary for the formation of endosome from which TLR9 signals to induce type I IFNs.
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Role of Mouse and Human Autophagy Proteins in IFN-γ-Induced Cell-Autonomous Responses against Thxoplasma gondii2014
Author(s)
Jun Ohshima, Youngae Lee, Miwa Sasai, Tatsuya Saitoh, Ji Su Ma, Naganori Kamiyama, Yoshiharu Matsuura, Suh Pann-Ghill, Mikako Hayashi, Shigeyuki Ebisu, Kiyoshi Takeda, Shizuo Akira, and Masahiro Yamamoto.
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Journal Title
The Journal of Immunology
Volume: 192(7)
Issue: 7
Pages: 3328-35
DOI
Related Report
Peer Reviewed / Open Access
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