Enhanced phenotypic and functional maturation of monocyte-derived dendritic cells from patients with active Crohn's...

Disturbed immunoregulation and an inappropriate immune response to gut microflora is assumed to be involved in the pathogenesis of inflammatory bowel disease (IBD). Physiologically dendritic cells (DCs) as the professional antigen presenting cells play a crucial role in the control of intestinal inflammation and immune tolerance. In order to evaluate their role in the IBD we analyzed the phenotypic and functional properties of monocyte-derived DCs (MoDCs) generated from UC and CD patients following stimulation with TNF-α, lipopolisaccharide E. coli or hydrocortisone. Thirty seven patients with moderate to severe inflammation (19 UC, 18 CD) were recruited to the study. Monocyte-derived dendritic cell immunophenotypes and their endocytic ability were analysed by flow cytometry and confocal microscopy, IL-6, IL-10, IL-12 and IL-23 secretion were investigated by ELISA. Both unstimulated and stimulated MoDCs generated from IBD patients had more mature phenotype and secreted elevated concentrations of proinflammatory cytokines as compared to a control group. The addition of LPS E. coli to culture media was associated with enhanced dendritic cell activation and maturation as compared to DCs stimulated only with TNF-α. This may suggest altered dendritic cell interactions with intestinal microflora in inflammatory bowel disease. Hydrocortisone decreases the numbers of mature dendritic cells and the proinflammatory cytokine concentrations in all cell culture types that may explain the efficacy of steroid therapy in inflammatory bowel disease.