2020 Fiscal Year Annual Research Report
Uncovering a novel therapeutic target for BMT-induced inflammation
Project/Area Number |
19K23837
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Research Institution | Hokkaido University |
Principal Investigator |
劉 知昇 北海道大学, 医学研究院, 助教 (30843437)
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | GVHD / NLRC5 / Therapeutic target |
Outline of Annual Research Achievements |
During the program, my research has progressed with scientific significance. The detailed achievements are described below. The goal of the 1st year's program is to determine whether NLRC5 regulates GVHD pathogenesis using in vivo mouse model. I have confirmed that compared to wild-type mice proliferation of the donor-derived CD8 T cells was significantly reduced CD8 T cell number with reduced inflammatory cytokines in NLRC5 KO mice using the GVHD-induced mouse model. Therefore, I concluded that NLRC5 is a critical factor for bone marrow transplantation-induced inflammation leading to the GVHD-mediated pathogenesis. Based on the first year's results, I further proceeded 2nd year's program. The goal of 2nd year's study is to identify the underlying mechanism of the NLRC5-mediated GVHD pathogenesis. I have confirmed that the activation of allogenic T cells is NLRC5-dependent using an ex-vivo culture system using allogeneic T cells with mixed lymphocytes. As a result, I could confirm that allogeneic T cell activation was dependent on NLRC5 expression level in Dendritic cells, and elimination of NLRC5 in DC showed significantly reduced T cell activation, inflammatory cytokine production, and tissue damage. Thus, altogether I concluded that NLRC5 is a key regulatory factor of the GVHD-derived pathogenesis. Moreover, my research suggests that targeting NLRC5 could be a potential therapeutic target for GVHD-induced inflammatory diseases such as organ rejection. Based on these achievements, currently I am preparing for publication.
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