the cxcr3(+)cd56bright phenotype characterizes a distinct nk cell subset with anti-fibrotic potential that shows dys-regulated activity in hepatitis ccxcr3(+)cd56bright表型特征明显的nk细胞子集与anti-fibrotic潜在表明丙型肝炎dys-regulated活动.pdfVIP

The CXCR3(+)CD56Bright Phenotype Characterizes a Distinct NK Cell Subset with Anti-Fibrotic Potential That Shows Dys-Regulated Activity in Hepatitis C ¨ ¨ ¨ Marianne Eisenhardt, Andreas Glassner, Benjamin Kramer, Christian Korner, Bernhard Sibbing, Pavlos Kokordelis, Hans Dieter Nischalke, Tilman Sauerbruch, Ulrich Spengler, Jacob Nattermann* Department of Internal Medicine I, University of Bonn, Bonn, Germany Abstract Background: In mouse models, natural killer (NK) cells have been shown to exert anti-fibrotic activity via killing of activated hepatic stellate cells (HSC). Chemokines and chemokine receptors critically modulate hepatic recruitment of NK cells. In hepatitis C, the chemokine receptor CXCR3 and its ligands have been shown to be associated with stage of fibrosis suggesting a role of these chemokines in HCV associated liver damage by yet incompletely understood mechanisms. Here, we analyzed phenotype and function of CXCR3 expressing NK cells in chronic hepatitis C. Methods: Circulating NK cells from HCV-infected patients (n = 57) and healthy controls (n = 27) were analyzed with respect to CXCR3 and co-expression of different maturation markers. Degranulation and interferon-c secretion of CXCR3(+) and CXCR3( 2) NK cell subsets were studied after co-incubation with primary human hepatic stellate cells (HSC). In addition, intra-hepatic frequency of CXCR3(+) NK cells was correlated with stage of liver fibrosis (n = 15). Results: We show that distinct NK cell subsets can be distinguished based on CXCR3 surface expression. In healthy controls CXCR3(+)CD56Bright NK cells displayed strongest activity against HSC. Chronic hepatitis C was associated with a significantly increased frequency of CXCR3(+)CD56Bright NK cell