2011年1月，我室生物大分子结构与功能研究部田志刚教授研究组在HEPATOLOGY上发表题为Hypercytolytic Activity of Hepatic Natural Killer Cells Correlates With Liver Injury in Chronic Hepatitis B Patients的论文。

Source: HEPATOLOGY Volume: 53 Issue: 1 Pages: 73-85 Published: JAN 2011

Zhang Z (Zhang, Zheng)1, Zhang SY (Zhang, Shuye)1, Zou ZS (Zou, Zhengsheng)2, Shi JF (Shi, Jianfei)1, Zhao JJ (Zhao, Juanjuan)1, Fan R (Fan, Rong)2, Qin EQ (Qin, Enqiang)2, Li BS (Li, Baosen)2, Li ZW (Li, Zhiwei)2, Xu XS (Xu, Xiangsheng)1, Fu JL (Fu, Junliang)1, Zhang JY (Zhang, Jiyuan)1, Gao B (Gao, Bin)3, Tian ZG (Tian, Zhigang)4,5, Wang FS (Wang, Fu-Sheng)1
Addresses:
1. Beijing 302 Hosp, Res Ctr Biol Therapy, Beijing 100039, Peoples R China
2. Beijing 302 Hosp, Dept Infect Dis, Beijing 100039, Peoples R China
3. NIAAA, NIH, Lab Liver Dis, Bethesda, MD USA
4. Univ Sci & Technol China, Inst Immunol, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Peoples R China
5. Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China
E-mail Addresses: fswang@public.bta.net.cn

Reprint Address: Wang, FS (reprint author), Beijing 302 Hosp, Res Ctr Biol Therapy, 100 Xi Si Huan Middle Rd, Beijing 100039, Peoples R China

Abstract:
Natural killer (NK) cells are abundant in the liver and serve as a major innate immune component against microbial infection. Although NK cells have been implicated in inducing hepatocellular damage in patients with chronic hepatitis virus infections, the roles that hepatic NK cells play in chronic hepatitis B virus (HBV) infections remain obscure. In this study, we comprehensively characterized intrahepatic and peripheral NK cells and investigated their impact on liver pathology in a cohort of HBV-infected individuals; this cohort included 51 immune-activated (IA) patients, 27 immune-tolerant (IT) carriers, and 26 healthy subjects. We found that NK cells expressing NK receptors (activation receptors) preferentially accumulated in the livers of IA patients, in which they were activated and skewed toward cytolytic activity but without a concomitant increase in interferon-gamma production, in comparison with those of IT carriers and healthy subjects. Further analysis showed that the livers of IA patients, in comparison with those of IT and healthy subjects, expressed higher levels of interleukin-12 (IL-12), IL-15, and IL-18 in situ and lower levels of IL-10, which in vitro can induce the activation and degranulation of NK cells from healthy individuals. Finally, hepatic NK cells displayed more cytolytic activity than peripheral NK cells, and this was found to be positively correlated with the liver histological activity index and serum alanine aminotransferase levels in these IA patients. Conclusion: In IA patients, hepatic NK cells are activated and preferentially skew toward cytolytic activity, which depends on an imbalanced cytokine milieu and correlates with liver injury during chronic HBV infection. (HEPATOLOGY 2011;53:73-85)