2014 Fiscal Year Final Research Report
Novel regulatory mechanism of TLR7/8 by ssRNA
| Project/Area Number |
26670235
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SHIBATA Takuma 東京大学, 医科学研究所, 助教 (30554505)
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| Project Period (FY) |
2014-04-01 – 2015-03-31
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| Keywords | 自然免疫 / TLR7 / TLR8 / 一本鎖核酸 |
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| Outline of Final Research Achievements |
Toll-like receptor 7 (TLR7) and 8 were considered to recognize single-strand RNA (ssRNA). Although these receptors also respond to synthetic small chemical ligands, such as CL075 and R848, it remains to be determined whether these receptors sense natural small molecules or not. We find that TLR7 work as the sensor for guanosine (G) /2’-deoxyguanosine (dG) in the presence of ORN where ORN strengthens TLR7 interaction with G/dG. In addition, modified nucleosides such as 7-methylguanosine, 8-hydroxyguanosine and 8-hydroxydeoxyguanosine (8-OHdG), activated TLR7 with ORNs. Importantly, 8-OHdG -a well-known oxidative DNA damage marker with unknown function- induced strong cytokine production comparable to G and dG both in mouse and human immune cells. Our results shed light on the biological function of guanosine and modified guanosines in innate immune response.
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| Free Research Field |
免疫学
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