Exploring the mechanisms how the loss of tolerance against nuclear autoantigens leads to development of SLE

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nara Medical University
• Principal Investigator: Miyagawa Fumi 奈良県立医科大学, 医学部, 講師 (00346024)
• Co-Investigator(Kenkyū-buntansha): 浅田 秀夫 奈良県立医科大学, 医学部, 教授 (60252681)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: SLE / IRF / type I IFN / NF-kB

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.

Free Research Field

皮膚免疫学