Characteristics of intestinal dendritic cells in inflammatory bowel diseases.
OBJECTIVE
Dendritic cells (DCs) recognize and respond to microbial structures using pattern recognition receptors, including Toll-like receptors (TLRs). In the intestine, DCs are pivotal in tolerance induction and direct the differentiation of T cells. We aimed to identify changes in intestinal DCs that may underlie the dysregulated immune response to enteric bacteria that occurs in patients with inflammatory bowel disease (IBD).


METHODS
DCs were identified in freshly isolated lamina propria mononuclear cells by multicolor flow cytometry in patients with IBD and controls. Expression of TLR2, TLR4, and the activation/maturation marker CD40 was assessed by cell surface labeling. Production of cytokines (interleukin [IL]-12, IL-6, and IL-10) was assessed in the absence of exogenous stimulation by intracellular staining of permeabilized cells.


RESULTS
In healthy controls, few intestinal DCs expressed TLR2 or TLR4, in contrast to blood DCs. DC expression of both TLRs was significantly enhanced in Crohn's disease and ulcerative colitis. DCs from inflamed tissue of patients with Crohn's disease expressed significantly higher levels of the maturation/activation marker CD40. Elevated levels of CD40 on DCs were decreased after treating patients with anti-tumor necrosis factor alpha. In Crohn's disease, but not ulcerative colitis, more colonic DCs produced IL-12 and IL-6. The number of IL-10-producing DCs did not differ significantly between patients with IBD and controls.


CONCLUSIONS
In IBD, DCs are activated, their expression of microbial recognition receptors is up-regulated, and more DCs produce pathologically relevant cytokines. Intestinal DCs are likely to be key initiators or perpetuators of the inflammatory response that characterizes IBD.
Hart
Ailsa L
AL
Antigen Presentation Research Group, Imperial College London, England.
Al-Hassi
Hafid Omar
HO
Rigby
Rachael J
RJ
Bell
Sally J
SJ
Emmanuel
Anton V
AV
Knight
Stella C
SC
Kamm
Michael A
MA
Stagg
Andrew J
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D019013:CD40 Antigens / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D015415:Biomarkers; D019013:CD40 Antigens; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016753:Interleukin-10; D018664:Interleukin-12