Characterization of antigen-presenting dendritic cells in the peripheral blood and colonic mucosa of patients with ulcerative colitis.
OBJECTIVE
Increased lymphocyte activation and production of inflammatory cytokines are implicated in the pathogenesis of ulcerative colitis. Because antigen-presenting dendritic cells play a cardinal role in the activation and survival of activated lymphocytes, the aim of the present study was to characterize dendritic cells in ulcerative colitis.


METHODS
This study was designed to compare the phenotypes and functions of peripheral blood dendritic cells among healthy normal volunteers and patients with ulcerative colitis or Crohn's disease. Activated dendritic cells were also localized at the colonic mucosa.


METHODS
Peripheral blood dendritic cells were generated from 15 patients with ulcerative colitis, 10 patients with Crohn's disease and 15 healthy control volunteers. The stimulatory capacities of dendritic cells were analysed in an allogenic mixed lymphocyte reaction. Nitric oxide was detected by the Griess method. Single- and dual-colour flow cytometry was employed to study the levels of maturation of dendritic cells. Activated dendritic cells were localized immunohistochemically in the colonic mucosa.


RESULTS
In comparison to normal controls, peripheral blood dendritic cells from patients with ulcerative colitis showed significantly increased stimulatory capacities (P < 0.05) and produced significantly higher levels of nitric oxide (P < 0.05). The numbers of activated dendritic cells were also significantly higher in ulcerative colitis (P < 0.05). Mature and activated dendritic cells expressing the CD83 antigen were detected at the inflamed colonic mucosa in patients with ulcerative colitis and Crohn's disease.


CONCLUSIONS
Activated and mature dendritic cells may have a role in the induction of an exacerbated immune response in ulcerative colitis. This study provides the scientific and logical basis for blocking the maturation and activation of dendritic cells in ulcerative colitis as a new therapeutic intervention.
Ikeda
Y
Y
Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-Cho, Ehime, Japan.
Akbar
F
F
Matsui
H
H
Onji
M
M
D000328:Adult; D015703:Antigens, CD; D051940:B7-2 Antigen; D003093:Colitis, Ulcerative / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens; D006801:Humans; D007136:Immunoglobulins; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008562:Membrane Glycoproteins; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009569:Nitric Oxide; D000097802:CD83 Antigen; C497964:CD86 protein, human