Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases.
OBJECTIVE
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.
Kunitani
Hitoshi
H
The Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Shimizu
Yukihiro
Y
Murata
Hiroyuki
H
Higuchi
Kiyohiro
K
Watanabe
Akiharu
A
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015703:Antigens, CD / Q000032:analysis; D051940:B7-2 Antigen; D039521:CD11c Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D002908:Chronic Disease; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007150:Immunohistochemistry; D016130:Immunophenotyping; D053650:Interleukin-3 Receptor alpha Subunit; D008099:Liver / Q000737:chemistry* / Q000166:cytology*; D008107:Liver Diseases / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D016185:Receptors, Interleukin-3 / Q000032:analysis; D000097802:CD83 Antigen
D000410:Alanine Transaminase; D015703:Antigens, CD; D051940:B7-2 Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D053650:Interleukin-3 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D016185:Receptors, Interleukin-3; D000097802:CD83 Antigen; C497964:CD86 protein, human; C115022:IL3RA protein, human