The mechanism of autoantibody production in IBD

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460946
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Oshima Shigeru 東京医科歯科大学, 医学部附属病院, 助教 (50376787)
• Co-Investigator(Kenkyū-buntansha): WATANABE Mamoru 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 炎症性腸疾患 / オートファジー / 自己抗体

Outline of Final Research Achievements

Polymorphisms in the human TNFAIP3 gene (which encodes A20 protein) are associated with reduced function or expression of A20 that confers susceptibility to Crohn’s disease. Autophagy plays important roles in autoantibody production. To determine whether A20 regulates autophagy in CD4 T cells, we analyzed A20 deficient CD4 T cells in vitro. We demonstrated that A20 deficient CD4 T cells exhibited reduced LC3 puncta formation, increased mitochondrial content, and exaggerated reactive oxygen species (ROS) production. These results indicate that A20 promotes autophagy after T cell receptor (TCR) stimulation in CD4 T cells. We found that A20-deficient T cells and fibroblasts were susceptible to caspase-independent and kinase RIPK3-dependent necroptosis. And also we demonstrated that RIPK3 interacts with p62 and regulates p62-LC3 complex formation.

Free Research Field

消化器内科