2005 Fiscal Year Final Research Report Summary
Natural killer receptor-mediated regulation of dendritic cell functions in chronic hepatitis C
| Project/Area Number |
16390207
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
TAKEHARA Tetsuo Osaka University, Graduate School of Medicine Department of Gastroenterology and Hepatology, Associate Professor, 医学系研究科, 助教授 (70335355)
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| Co-Investigator(Kenkyū-buntansha) |
KANTO Tatsuya Osaka University, Graduate School of Medicine Department of DC Biology and Clinical Application, Endowed Chair Associate Professor, 医学系研究科, 寄附講座助教授 (80372613)
TATSUMI Tomohide Osaka University, Graduate School of Medicine Department of Gastroenterology and Hepatology, Specially Appointed Assistant, 医学系研究科, 特任助手(常勤) (20397699)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Immunology / Cancer / Liver / NK cell / Hepatitis C / Innate immunity / Liver cancer / Virus |
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| Research Abstract |
Natural kilier (NK) cells are specialized lymphocytes that provide a first line of defense through their ability to kill pathogen-infected cells and transformed cells. The function of NK cells is regulated by a fine balance of inhibitory and activating signals, which are mediated by a diverse array of cell-surface receptors. We recently found that expression of the inhibitory receptor CD94/NKG2A is upregulated on NK cells in patients with chronic hapatitis C. HLA-E, a ligand for NKG2A, was expressed in all human hepatoma cell lines tested as well as non-transformed hepatocytes, but not in K562 cells, a classical NK-sensitive target. NK cells isolated from patients with chronic hepatitis C (HCV-NK) were less capable of killing hepatoma cells and of producing IFNγ in response to hepatoma cells than those from healthy donors, whereas there was no significant difference in NK responsiveness towards K562 cells. Of note is the finding that maturation and activation of monocyte-derived dendritic cells were negatively modulated in the presence of HCV-NK and hepatoma cells, which was restored by the addition of anti-NKG2A antibody during the coculture of HCV-NK and hepatoma cells. Research revealed that dendritic cells recognize danger signals from microorganisms by monitoring pathogen-associated molecular patterns via Toll-like receptors. Our findings have shed light on NK receptors as an important interface that transmits danger signals from abnormal cells to immune systems. Aberrant expression of CD94/NKG2A should have negative impact on innate resistance and subsequent adaptive immunity towards HCV-infected or transformed cells in chronic hepatitis C.
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[Journal Article] Concanavarin A injection activates intrahepatic innate immune cells to provoke an anti-tumor effect in murine liver.2004
Author(s)
Miyagi T, Takehara T, Tatsumi T, Suzuki T, Jinushi M, Kanazawa Y, Hiramatsu N, Kanto T, Tsuji S, Hori M, Hayashi N.
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Journal Title
Hepatology 40
Pages: 1190-1196
Description
「研究成果報告書概要(欧文)」より
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