title: Interleukin-21 mediates hepatitis B virus-associated liver cirrhosis by activating hepatic stellate cells.
abstract: OBJECTIVE
  Interleukin-21 (IL-21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL-21 in HBV-associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL-21 in HBV-associated liver cirrhosis and possible mechanisms.
  
  
  METHODS
  The study subjects included 10 healthy controls and 30 patients with HBV-associated liver cirrhosis that categorized into three subgroups based on Child-Pugh score (A, 13; B, 10; C, 7). The frequencies of IL-21(+) CD4(+) T cells were detected by flow cytometry, and the level of IL-21 in plasma was measured by enzyme-linked immunoassay. The distribution of IL-21(+) cells in situ in liver was observed by immunohistochemistry. In addition, the in vitro expression of α-smooth muscle actin (α-SMA), apoptosis and proliferation markers of LX-2 cells were examined by flow cytometry and Cell Counting Kit-8 kit. Finally, the collagen levels in the supernatant were measured by chemiluminescence.
  
  
  RESULTS
  Increased peripheral number of IL-21(+) CD4(+) cells, elevated plasma level of IL-21 and IL-21(+) cell accumulation in liver were observed in patients with HBV-associated liver cirrhosis. In vitro administration of IL-21 was accompanied with increased expression of α-SMA, inhibited LX-2 cells apoptosis and upregulated collagen production by LX-2 cells.
  
  
  CONCLUSIONS
  IL-21 may contribute to the fibrogenesis of HBV-associated liver cirrhosis by activating the hepatic stellate cells. Therefore, neutralization of IL-21 could be a favorable new therapeutic strategy for liver cirrhosis treatment.
authors.affiliation: Institute of Translational Hepatology, Beijing 302 Hospital, Peking University Health Science Center, Beijing, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Feng
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Qing-Lei
authors.initials: QL
authors.lastname: Zeng
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Sa
authors.initials: S
authors.lastname: Lv
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xu
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
keywords: hepatic stellate cell; hepatitis B virus-associated liver cirrhosis; interleukin-21