Article

Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics

Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
Hepatology (Impact Factor: 11.19). 01/2013; 57(1). DOI: 10.1002/hep.26016
Source: PubMed

ABSTRACT Liver fibrosis is a wound healing response to chronic liver injury and inflammation in which macrophages and infiltrating monocytes participate in both the development and resolution phase. In humans, three monocyte subsets have been identified: the classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. We studied the phenotype and function of these monocyte subsets in peripheral blood and liver tissue from patients with chronic inflammatory and fibrotic liver diseases. The frequency of intrahepatic monocytes increased in disease compared with control liver tissue and in both non-diseased and diseased livers there was a higher frequency of CD14++CD16+ cells with blood. Our data suggest two non-exclusive mechanisms of CD14++CD16+ accumulation in the inflamed liver: 1) recruitment from blood because more than twice as many CD14++CD16+ monocytes underwent transendothelial migration through hepatic endothelial cells compared with CD14++CD16- cells 2) local differentiation from CD14++CD16- classical monocytes in response to TGFβ and IL-10. Intrahepatic CD14++CD16+ cells expressed both macrophage and dendritic cell markers but showed high levels of phagocytic activity, antigen presentation and T cell proliferation and secreted pro-inflammatory (TNFα, IL-6, IL-8, IL-1β) and pro-fibrogenic cytokines (IL-13), chemokines (CCL1, CCL2, CCL3, CCL5), and growth factors (G-CSF and GM-CSF), consistent with a role in the wound healing response. CONCLUSION: Intermediate CD14++CD16+ monocytes preferentially accumulate in chronically inflamed human liver as a consequence of enhanced recruitment from blood and local differentiation from classical CD14++CD16- monocytes. Their phagocytic potential and ability to secrete inflammatory and pro-fibrogenic cytokines suggests they play an important role in hepatic fibrogenesis. (HEPATOLOGY 2012.).

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