| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Outline of Final Research Achievements |
The following experiments were conducted to clarify the in vivo roles of the biosynthetic enzyme (LTA4H) and receptors (BLT1 and BLT2) for the biologically active lipid leukotriene B4(LTB4). We generated dendritic cell (DC)-specific BLT1-deficient mice, and LTA4H E297Q knock-in mice lacking only aminopeptidase activity. Using these mice, I obtained the following results 1) I identified dendritic cell subsets defined by BLT1 expression and determined their different roles in inflammatory disease models. BLT1-high DC enhances inflammation by staying at the inflammatory lesion and secreting IL-12, and BLT1-low DC migrates to draining lymph node and stimulates T cell proliferation by secreting IL-2. 2) In LTA4H-deficient mice, thyroid hormone secretion is increased, resulting in a "thin" phenotype, which is dependent on the loss of aminopeptidase activity of LTA4H, not on the loss of LTB4-producing activity. LTA4 aminopeptidase activity somehow inhibits thyroid hormones production/release.
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