Exploring the mechanisms how the loss of tolerance against nuclear autoantigens leads to development of SLE
| Project/Area Number |
15K09779
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Nara Medical University |
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Principal Investigator |
Miyagawa Fumi 奈良県立医科大学, 医学部, 講師 (00346024)
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| Co-Investigator(Kenkyū-buntansha) |
浅田 秀夫 奈良県立医科大学, 医学部, 教授 (60252681)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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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| Keywords | SLE / IRF / type I IFN / NF-kB / IRF7 / IRF8 / 炎症性単球 / 抗核抗体 / I型IFN |
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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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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Preferential expression of CD134, an HHV-6 cellular receptor, on CD4 T cells in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS).2016
Author(s)
Miyagawa F, Nakamura Y, Miyashita K, Iioka H, Himuro Y, Ogawa K, Nishimura C, Nishikawa M, Mitsui Y, Ito Y, Ommori Rie, Mori Y, Asada H
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Journal Title
J Dermatol Sci
Volume: 83
Issue: 2
Pages: 151-154
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Differential expression profile of Th1/Th2-associated chemokines characterizes Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug-induced hypersensitivity syndrome /drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) as distinct entities.2015
Author(s)
Miyagawa F, Hasegawa A, Imoto K, Ogawa K, Kobayashi N, Ito K, Fujita H, Aihara M, Watanabe H, Sueki H, Tohyama M, Asada H
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Journal Title
Eur J Dermatol
Volume: 25
Issue: 1
Pages: 87-9
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Efficacy of additional i.v. immunoglobulin to steroid therapy in Stevens-Johnson syndrome and toxic epidermal necrolysis.2015
Author(s)
Aihara M, Kano Y, Fujita H, Kambara T, Matsukura S, Katayama I, Azukizawa H, Miyachi Y, Endo Y, Asada H, Miyagawa F, Morita E, Kaneko S, Abe R, Ochiai T, Sueki H, Watanabe H, Nagao K, Aoyama Y, Sayama K, Hashimoto K, Shiohara T; SJS/TEN Study Group.
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Journal Title
J Dermatol
Volume: 42
Issue: 8
Pages: 768-777
DOI
Related Report
Peer Reviewed / Open Access
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