Characterization and distribution of colonic dendritic cells in Crohn's disease.
Dendritic cells (DCs) are thought to play an important role in the pathogenesis of autoimmune inflammation, including Crohn's disease (CD). We investigated the distribution and state of maturation of DCs in the colon in relation to the severity of inflammation and therapy. Using archival specimens from colonic resections in 19 pediatric patients with CD and 14 controls, we identified and characterized the DCs within the lamina propria, submucosa, and muscularis compartments using morphologic and quantitative immunohistochemical methods. The distribution of CD11c+CD83+CD68+DC-SIGN+ and immature CD11c+CD83-CD68-DC-SIGN+ DCs within the different compartments varied according to the presence or absence of CD as well as to the severity of inflammation and systemic corticoid treatment. Immature DCs were only found in non-inflamed control colonic tissue. Marked reductions (60% and 30%) in total CD11c and CD83 DC numbers were observed in CD tissue samples compared with controls (P < 0.05). CD samples from patients on corticosteroid therapy were significantly more depleted than in tissue from untreated patients or those on other drugs. Colonic tissue with severe inflammation had reduced numbers of CD11c+ and CD83+ DCs in the lamina propria and submucosal compartments (80% and 76% for CD11c; 75% and 76% for CD83, respectively, P < 0.05), with a concomitant increase (525% for CD11c and 700% for CD83 P < 0.05) of DCs in the muscularis compartment, compared to moderately inflamed and non-inflamed CD tissue. Our data suggest that an imbalance in intestinal DC subpopulations may play a role in the initiation and/or the maintenance of chronic inflammation in CD. Corticosteroid therapy is associated with colonic DC depletion.
Mucosal Immunology Laboratory, Division of Gastroenterology, Hepatology & Nutrition, Sainte-Justine Hospital Research Centre, Department of Paediatrics, University of Montreal, Quebec, Canada H3TICS.
Manuel A
MA
Silva
Carolina B
CB
López
Francine
F
Riverin
Luc
L
Oligny
José
J
Menezes
Ernest G
EG
Seidman
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D015703:Antigens, CD; D018845:CD11 Antigens / Q000032:analysis; D016022:Case-Control Studies; D002454:Cell Differentiation; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D003713:Dendritic Cells; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007249:Inflammation / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D012720:Severity of Illness Index; D000097802:CD83 Antigen
D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D018845:CD11 Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen