Analysis of Regulatory B cell Distribution and Function in Primary Biliary Cirrhosis (Cholangitis) Model Mice and Optimization of B cell Targeted Therapy

• Project/Area Number: 24590952
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Akita University
• Principal Investigator: Moritoki Yuki 秋田大学, 医学部, 講師 (90585522)
• Co-Investigator(Kenkyū-buntansha): CHIHARA Junichi 秋田大学, 医学(系)研究科(研究院), 教授 (80197615)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 原発性胆汁性肝硬変(原発性胆汁性胆管炎) / B細胞 / IL-10 / PBC / 炎症制御細胞 / 動物モデル / 原発性胆汁性肝硬変 / マウスモデル

Outline of Final Research Achievements

We have conducted a model mice study of human Primary Biliary Cirrhosis (Cholangitis) to propose a highly effective and safe therapeutic strategy using regulatory B cells. In order to identify and analyze regulatory B cells that produce Interleukin (IL)-10, one of the immunosuppressive cytokines, IL-10-GFP reporter mice were crossed with the model mice of Primary Biliary Cirrhosis (Cholangitis) to develop IL-10-GFP expressing model mice. The developed model mice demonstrated liver inflammation histopathologically, serum positivity of anti-mitochondrial autoantibody, and elevated levels of total IgA and IgG, which were equivalent to those found in the original model mice. In addition, it was revealed that distribution of IL-10 producing regulatory B cells differ extremely among the physical areas.

Research Products

• [Journal Article] Splenic lymph follicles generate immunoglobulin M-producing B cells in primary biliary cirrhosis. (2014)
  • Author(s): Kikuchi K, Tsuneyama K, Yamada H, Kajiyama Y, Matsumoto K, Tsunashima H, Yamashita R, Takai A, Negishi M, Hara M, Moritoki Y, Miyakawa H.
  • Journal Title: Hepatol Res. Volume: in press Issue: 10
  • DOI: 10.1111/hepr.12231
  • Peer Reviewed / Open Access
• [Presentation] B cell immunity in Primary Biliary Cirrhosis (2012)
  • Author(s): Yuki Moritoki
  • Organizer: First China-Japan Symposium on Autoimmune Liver Disease
  • Place of Presentation: Hefei, China
  • Invited