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 Crohns disease) were included in the study. Clinical activity of the disease was assessed by the Pediatric Ulcerative Colitis Activity Index and the Pediatric Crohns 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 Crohns 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.
Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Medical University of Gdańsk, Poland.
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Sznurkowska
Department of Pathology, Medical University of Gdańsk, Poland.
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Żawrocki
Department of Surgical Oncology, Medical University of Gdańsk, Poland.
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Sznurkowski
Department of Pathology and Neuropathology, Medical University of Gdańsk, Poland.
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Iżycka-Świeszewska
Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Medical University of Gdańsk, Poland.
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Landowski
Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Medical University of Gdańsk, Poland.
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Szlagatys-Sidorkiewicz
Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Medical University of Gdańsk, Poland.
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Plata-Nazar
Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Medical University of Gdańsk, Poland.
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Kamińska
D000293:Adolescent; D016022:Case-Control Studies; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase