BACKGROUND: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, yet little is known about the intrahepatic immune response in end-stage patients. Chemokines and their receptors are important regulators of immunity, particularly in the migration and localization of circulating leukocytes within peripheral tissues. AIMS: This report provides a comprehensive comparison of the chemokine receptor and activation phenotype of the major leukocyte subsets present in end-stage HCV-infected and non-HCV infected livers. METHODS: Lymphocytes were purified from homogenized explant liver tissue and analyzed by flow cytometry. RESULTS: NK cells are the predominant cell type, followed by T cells, B cells and NK-T cells, independent of HCV status. T cells displayed a memory phenotype and low levels of activation markers. CCR5, CXCR3 and CXCR6 were expressed on a large fraction of activated cells, while moderate to low expression of CCR2, CCR6 and CX(3)CR1 was observed. Several other tissue-specific and inflammatory chemokine receptors were absent from infiltrating lymphocytes. CONCLUSIONS: These results identify the chemokine receptors present on infiltrating lymphocytes during end-stage liver disease and suggest that such infiltration is predominantly controlled by non-tissue-specific inflammatory chemokines, a situation that may be distinct from liver homing pathways under normal conditions.
BACKGROUND:Hepatitis C virus (HCV) is a leading cause of chronic liver disease, yet little is known about the intrahepatic immune response in end-stage patients. Chemokines and their receptors are important regulators of immunity, particularly in the migration and localization of circulating leukocytes within peripheral tissues. AIMS: This report provides a comprehensive comparison of the chemokine receptor and activation phenotype of the major leukocyte subsets present in end-stage HCV-infected and non-HCV infected livers. METHODS: Lymphocytes were purified from homogenized explant liver tissue and analyzed by flow cytometry. RESULTS: NK cells are the predominant cell type, followed by T cells, B cells and NK-T cells, independent of HCV status. T cells displayed a memory phenotype and low levels of activation markers. CCR5, CXCR3 and CXCR6 were expressed on a large fraction of activated cells, while moderate to low expression of CCR2, CCR6 and CX(3)CR1 was observed. Several other tissue-specific and inflammatory chemokine receptors were absent from infiltrating lymphocytes. CONCLUSIONS: These results identify the chemokine receptors present on infiltrating lymphocytes during end-stage liver disease and suggest that such infiltration is predominantly controlled by non-tissue-specific inflammatory chemokines, a situation that may be distinct from liver homing pathways under normal conditions.
Authors: M M Gaida; F Günther; C Wagner; H Friess; N A Giese; J Schmidt; G M Hänsch; M N Wente Journal: Clin Exp Immunol Date: 2008-09-05 Impact factor: 4.330
Authors: Liping Zhang; Limei Ran; Gabriela E Garcia; Xiaonan H Wang; Shuhua Han; Jie Du; William E Mitch Journal: Am J Pathol Date: 2009-11-05 Impact factor: 4.307
Authors: Todd Bartkowiak; Ashvin R Jaiswal; Casey R Ager; Renee Chin; Chao-Hsien Chen; Pratha Budhani; Midan Ai; Matthew J Reilley; Manu M Sebastian; David S Hong; Michael A Curran Journal: Clin Cancer Res Date: 2018-01-04 Impact factor: 12.531