Indoleamine 2,3-dioxygenase and regulatory t cells in intestinal mucosa in children with inflammatory bowel disease.

Impaired immune regulation has been suggested as an underlying mechanism of inflammatory bowel disease. Indoleamine 2,3-dioxygenase (IDO) and regulatory T cells expressing FOXP3 are crucial elements of immune regulation. Conversion of FOXP3- lymphocytes to Tregs is one of the functions of IDO. The aim of this study was to evaluate the number of cells expressing FOXP3 and IDO in the lamina propria of intestinal mucosa and to evaluate correlations between these parameters and disease activity. Sixty-six children newly diagnosed with inflammatory bowel disease (41 patients with ulcerative colitis and 25 patients with Crohn’s disease) were included in the study. Clinical activity of the disease was assessed by the Pediatric Ulcerative Colitis Activity Index and the Pediatric Crohn’s Disease Activity Index. Histopathological activity was scored according to the system described by Geboes. The infiltration of FOXP3+ and IDO+ cells was evaluated by immunohistochemistry. Sixteen patients with a diagnosis of irritable bowel syndrome (IBS) served as a control group. Lamina propria demonstrated a significantly higher infiltration of FOXP3+ and IDO+ cells in inflammatory bowel disease compared to the control group (p=0.001, p=0.004, respectively). The number of IDO+ and FOXP3+ cells correlated with clinical and histopathologic activity of Crohn’s disease. A positive correlation between the number of IDO+ and FOXP3+ cells was found in both types of inflammatory disease but not in patients with IBS. We conclude that indoleamine dioxygenase and FOXP3+ cells are upregulated in the intestinal mucosa of children with inflammatory bowel disease. IDO mediated conversion of FOXP3 -T cells to Tregs predominantly occurs in inflammation.