CD83+CCR7- dendritic cells accumulate in the subepithelial dome and internalize translocated Escherichia coli HB101 in the Peyer's patches of ileal Crohn's disease.
Recurrent Crohn's disease originates with small erosions in the follicle-associated epithelium overlying the Peyer's patches. Animal studies have illustrated mucosal immune regulation by dendritic cells located in the subepithelial dome. The aim of this study was to characterize the dendritic cells at this specific site in patients with Crohn's disease. Ileal tissues were obtained after surgery performed on Crohn's patients; ileal samples from noninflammatory bowel disease and ulcerative colitis served as standard and inflammatory controls, respectively. Flow cytometry of isolated intestinal mononuclear cells showed a larger subset of dendritic cells in Crohn's samples compared with controls. This finding was corroborated by confocal microscopy, showing enhanced infiltrates of cells positive for the dendritic cell markers, DC-SIGN(+) and CD83(+), in the subepithelial dome. Moreover, the CD83(+) cells in Crohn's tissues showed reduced expression of the lymph node migratory receptor, CCR7, possibly contributing to the high numbers of dendritic cells. After exposure to nonpathogenic Escherichia coli in Ussing chambers, dendritic cells in the subepithelial dome of Crohn's disease demonstrated increased co-localization with translocated bacteria. Immunohistochemical results revealed that DC-SIGN(+) cells in Crohn's tissues were found to express toll-like receptor 4 and produce tumor necrosis factor-alpha. In conclusion, nonmigrating dendritic cells that accumulate in the subepithelial dome and internalize nonpathogenic bacteria may be important for the onset and perpetuation of mucosal inflammation in Crohn's disease.
Salim
Sa'ad Y
SY
Divisions of Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Silva
Manuel A
MA
Keita
Asa V
AV
Larsson
Marie
M
Andersson
Peter
P
Magnusson
Karl-Eric
KE
Perdue
Mary H
MH
Söderholm
Johan D
JD
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D018988:Bacterial Translocation; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D004926:Escherichia coli / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D018613:Microscopy, Confocal; D008875:Middle Aged; D010581:Peyer's Patches / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D054400:Receptors, CCR7 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C515370:CCR7 protein, human; C495345:TLR4 protein, human