| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Outline of Final Research Achievements |
The aim of this study is to investigate how IL28B is involved in the IFN resistance in patients of chronic hepatitis C. Comparison of gene expression profiling in PBMC and liver showed that the loss of correlation of ISGs expression between PBMC and liver in IL28B minor patients. Laser capture micro dissection analysis (LCM) of hepatocyte and liver infiltrated lymphocytes combined with immune-staining of surface marker of immune cells showed that infiltration of lymphocyte into the liver was impaired in patients with IL28B minor patients. Interestingly, non-canonical wnt ligand, WNT5A was up-regulated in the liver of IL28B minor patients and WNT5A induced ISGs and stress granule protein G3BP1, and increased HCV replication. WN5A repressed the expression of chemokines and play roles in the impairment of lymphocytes infiltration in liver. The analysis of newly developed IL28B knockout mouse showed that IL28B was directly involved in the lymphocytes infiltration in liver.
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