| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
This study aimed to clarify the pathogenic role of anti-DNA antibodies which are produced specifically in systemic lupus erythematosus (SLE). A monoclonal antibody WB-6 was demonstrated to cross-react with beta-2-glycoprotein I and DNA. We found it binds to cell surface DNA, and enters live monocytes accompanying DNA, which results in activation of intracellular DNA sensors to induce expression of tissue factor. These results suggest a novel mechanism in pathogenesis of antiphospholipid syndrome accompanied by SLE. On the other hand, another monoclonal anti-DNA antibody 2C10, which is specific to double-stranded DNA and does not cross-react with beta-2-glycoprotein I, also entered live monocytes by endocytosis. As a result, it induced secretion of several proinflammatory cytokines which is known to be elevated in SLE via activation of the TLR9 and AIM2 signaling pathways. These results established a simple and useful assay system to reproduce a pathological state resembling SLE.
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