The pathogenesis of S1PR1 reduction via miR223-3p in Lupus T cells.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09896
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Okayama University
• Principal Investigator: WATANABE KATSUE (砂堀克枝) 岡山大学, 医学部, 客員研究員 (80639914)
• Research Collaborator: ASANO Sumie (Hiramatsu Sumie)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: SLE / S1PR1 / miR223 / T細胞

Outline of Final Research Achievements

The reduction of sphingosine 1 phosphate receptor 1 (S1PR1) expression in systemic lupus erythematosus (SLE) is reported. We confirmed the upregulation of microRNA223-3p (miR223), which suppresses the expression of S1PR1, in the splenic T cells in MRL/lpr lupus-prone mice. We constructed and analyzed miR223 knockout B6/MRL mice. The proportion of early apoptosis cells in peripheral lymphatic CD4+ T cells was significantly increased, and the numbers of CD19+ cells, CD19+CD138+ cells and CD138+ cells in spleen were also significantly increased. They might contribute to the improvement of the disease activity of SLE.

Free Research Field

リウマチ膠原病学

Academic Significance and Societal Importance of the Research Achievements

後天的遺伝子制御によりSLEの病態形成に関与する新規候補microRNAとしてmiR223-3pに着目し、標的遺伝子であるS1PR1の発現制御を介したアポトーシス能への影響等が確認された。SLEは、いまだアンメットメディカルニーズの高い難治性の自己免疫疾患であり、miR223及びS1PR1が新規治療標的となりえる可能性が示唆された。