A study of the innovative treatment for rheumatoid arthritis by regulating signal crosstalk via DcR3

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kobe University
• Principal Investigator: Miura Yasushi 神戸大学, 保健学研究科, 准教授 (60346244)
• Research Collaborator: FUKUDA Koji ; MAEDA Toshihisa
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 関節リウマチ / リウマチ滑膜線維芽細胞

Outline of Final Research Achievements

We newly found and reported that the expression of IL-12B(p40) was up-regulated by DcR3 specifically in rheumatoid fibloblast-like synovial fibroblasts (RA-FLS) in Molecular Medicine Reports. We also reported that Decoy receptor 3 down-regulates centrosomal protein 70kDa specifically in rheumatoid synovial fibroblasts in Modern Rheumatology. Further, we reported the expression profiling of genes in RA-FLS regulated by tumor necrosis factor-like ligand 1A in Biomedical Reports. Consequently, DcR3-TL1A signaling on RA synovial fibroblasts is shown as a possible new treatment target of RA.

Free Research Field

リウマチ学

Academic Significance and Societal Importance of the Research Achievements

TNFデコイ受容体であるDcR3により関節リウマチ(RA)滑膜線維芽細胞(FLS)において発現が制御される遺伝子のうち、IL-12B(p40)とCEP70がDcR3-TL1Aシグナル系におけるRA治療標的分子であること、ならびに、DcR3のリガンドであるTL1AによりRA-FLSにおいて発現が制御される一連の遺伝子を解明したことは、RAの新しい治療標的分子を明らかにした点で高い意義を有する。