| Budget Amount *help |
¥183,170,000 (Direct Cost: ¥140,900,000、Indirect Cost: ¥42,270,000)
Fiscal Year 2020: ¥35,100,000 (Direct Cost: ¥27,000,000、Indirect Cost: ¥8,100,000)
Fiscal Year 2019: ¥38,090,000 (Direct Cost: ¥29,300,000、Indirect Cost: ¥8,790,000)
Fiscal Year 2018: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000)
Fiscal Year 2017: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
Fiscal Year 2016: ¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
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| Outline of Final Research Achievements |
The lysosome is the site for nucleic acid (NA) metabolism, NA-sensing by Toll-like receptors (TLRs), and metabolite-sensing by mTORC1. We focused on the crosstalk among these processes. TLR7 and TLR3 induced lysosomal anterograde trafficking in a manner dependent on Arl8b or Rab7a, respectively. Such lysosomal trafficking enabled type I interferon induction through TLR interaction with mTORC1. We also studied the role of RNaseT2, the lysosomal RNase, in activation of RNA-sensing TLRs. RNase T2 negatively and positively regulated RNA-sensing TLRs probably through their ligand degradation or generation, respectively. These results demonstrate that NA metabolism and mTORC1 control NA-sensing TLRs. Dysregulation of the control causes human diseases such as histiocytosis.
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