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Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases
Hitoshi Kunitani1, Yukihiro Shimizu, Hiroyuki Murata
1The Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Background/Aims:
Dendritic cells (DCs) are the most potent professional antigen-presenting cells. Although two subsets of circulating DCs, lineage(-)CD11c(+)CD4(low) (CD11c(+)DCs) and lineage (-)CD11c(-)CD4(+)CD123(+) (CD123(+)DCs) are identified in humans, the role of each DC subset in the immunopathogenesis of liver diseases is unknown.
Methods:
We examined the numbers and activation status of each DC subset in the circulation and in the inflamed livers in patients with chronic liver diseases by flow cytometry and immunohistochemistry.
Results:
The numbers of circulating CD11c(+)DCs were inversely correlated with serum alanine aminotransferase (ALT) levels in patients with chronic viral hepatitis, and that the expression of costimulatory molecules on circulating CD11c(+)DCs in patients with chronic viral hepatitis was significantly up-regulated in patients with high serum levels of ALT. Both DCs are also identified in the livers by flow cytometry, and the expression of costimulatory molecule CD40 on those DCs was significantly higher in liver DCs than that in circulating DCs. Moreover, the ratios of CD11c(+)DCs/CD123(+)DCs were higher in liver DCs (mean+/-SD, 7.2+/-6.0) than those of circulating DCs (4.0+/-4.6). Immunohistochemically, CD11c(+) or CD123(+) cells and CD83(+) activated DCs were observed mostly in portal areas with mononuclear cell infiltration in various liver diseases. These overall data suggest that DCs, especially CD11c(+)DCs, could be associated with the necroinflammatory response in the liver of chronic viral liver diseases.
Conclusions:
DCs, especially CD11c(+)DCs, may be involved in the immunopathogenesis of chronic liver diseases.