Activated hepatic stellate cells impair NK cell anti-fibrosis capacity through a TGF-β-dependent emperipolesis in HBV cirrhotic patients

• DOI: 10.1038/srep44544
• Publication Date: 2017-03-14T15:42:33Z
• Authors: Jijing Shi; Juanjuan Zhao; Xin Zhang; Yongqian Cheng; Jinhua Hu; Yuanyuan Li; Xin Zhao; Qinghua Shang; Yanling Sun; Bo Tu; Lei Shi; Bin Gao; Fu-Sheng Wang; Zheng Zhang
• Keywords: Emperipolesis; Hepatic stellate cell; Hepatic fibrosis; Kupffer cell

Abstract Natural killer (NK) cells can induce liver fibrosis remission by killing hepatic stellate (HSCs) and producing interferon (IFN)-γ in a mouse model; however, their anti-fibrotic immune-characteristics regulatory mechanisms HSCs remain to be determined, especially livers from HBV-infected cirrhosis (LC) patients. We analyzed frequency, phenotype function of peripheral NK subsets 43 HBV-LC found that LC patients displayed decreased activation status activity compared with those chronic hepatitis B patients, which were mainly mediated increased intrahepatic tumour-growth factor (TGF)-β because blockade TGF-β significantly reversed vitro. In vivo , enriched proximity the α-smooth muscle actin (α-SMA+) area within mild regions; while severe fibrotic areas, they either directly attached or separated α-SMA+ region. could enter form emperipolesis (a cell-in-cell structure) become apoptotic; anti-TGF-β treatment ameliorated this emperipolesis. This finding suggested novel mechanism activated impair cells’ anti-fibrosis capacity through TGF-β-dependent providing an rational enhancing cell activity.