CD14⁺ monocyte‐derived galectin‿ induces natural killer cell cytotoxicity in chronic hepatitis C

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• 作者：Akira Nishio ; Tomohide Tatsumi ; Takatoshi Nawa ; Takahiro Suda ; Teppei Yoshioka ; Yoshiki Onishi ; Satoshi Aono ; Minoru Shigekawa ; Hayato Hikita ; Ryotaro Sakamori ; et al
• 刊名：Hepatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：65
• 期：1
• 页码：18-31
• 全文大小：1.0MB
• ISSN：1527-3350

文摘

Natural killer (NK) cell activation is associated with both liver injury and persistent infection in chronic hepatitis C (CHC); however, the detailed mechanism of this activation has not yet been fully elucidated. Because galectin-9 (Gal-9) has been reported to be increased in the serum and liver tissue of CHC patients, we investigated the function of Gal-9 in NK cell activation in CHC. First, we evaluated the function of Gal-9 on NK cytotoxicity in vitro. Gal-9 treatment resulted in increased cytotoxicity of naïve NK cells, and the Gal-9-activated NK cells demonstrated cytotoxicity toward hepatoma cells and T cells. Additionally, coculturing peripheral blood mononuclear cells (PBMCs) with JFH-1/Huh7.5.1 cells increased both Gal-9 production and NK cell cytotoxicity. Next, we investigated the source of Gal-9 and the mechanism of Gal-9 production. Deletion of CD14⁺ monocytes from PBMCs resulted in reduced Gal-9 production in the coculture with JFH-1/Huh7.5.1 cells. Gal-9 production was driven by coculturing of PBMCs with apoptotic hepatocytes. Blocking integrin α_vβ₃, a receptor for phosphatidylserine expressed on apoptotic cells, also resulted in decreased Gal-9 production. Finally, we found that serum Gal-9 levels were significantly higher in CHC patients than in healthy donors and patients who achieved sustained virologic response. Among CHC patients, serum Gal-9 levels were significantly higher in patients with elevated alanine aminotransferase (ALT) than in those with normal ALT. Conclusion: These results demonstrate that CD14⁺ monocyte-derived Gal-9 increases NK cell cytotoxicity in HCV infection, which might be associated with liver injury and persistent infection. (Hclass="smallCaps">epatology 2017;65:18-31).