| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| 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.
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