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

Research Project

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 *help	¥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.