| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
In this study, we investigated the role of IRF7 and IRF8 in the pathogenesis of SLE using a mouse model of SLE induced by pristane. SLE was chemically induced into IRF7 knockout (KO) mice and glomerulonephritis were observed after 10 months. However, these mice failed to produce autoantibodies. In contrast, following the chemical induction, IRF8KO mice showed no production of autoantibodies along with reduced glomerulonephritis. We found that inflammatory monocytes were recruited into the peritoneum as well as the kidney in wild-type and IRF7KO mice but not in IRF8KO mice after pristane injection. These inflammatory monocytes produced proinflammatory cytokines such as IL-6 and TNF-α, suggesting that they contribute to tissue damage. Our study suggests that type I IFN pathway seems critical for the autoantibody production but NF-κB-dependent proinflammatory cytokines produced from inflammatory monocytes are sufficient for the development of glomerulonephritis in this model.
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