[en] [en] OBJECTIVES: Regulatory T cells (TR cells) play a crucial role in the regulation of intestinal inflammation. To examine the pathogenetic relevance of TR cells in inflammatory bowel disease (IBD), we evaluated their frequency in peripheral blood and inflamed and noninflamed mucosae of pediatric patients with IBD and age-matched controls without IBD; we also characterized the immune profile of the inflammatory infiltrate in the different phases of the disease.
PATIENTS AND METHODS: Circulating TR cells were investigated on peripheral blood mononuclear cells by fluorescence-activated cell sorting analysis; mucosal TR cells and inflammatory cell populations were investigated by immunohistochemistry on bioptic specimens. FOXP3 messenger RNA expression levels were confirmed using real-time polymerase chain reaction.
RESULTS: FOXP3+ TR cells were significantly increased in the intestinal lesions of patients with active IBD, and returned to normal levels in posttherapy remission phase. At variance, circulating TR cell frequency was elevated in patients with IBD independently of disease activity, as it persisted in the remission phase. A selective imbalance in the frequency of CD4+ T and natural killer cell subsets characterized the abundant inflammatory infiltrate of active intestinal lesions, and also persisted, at a lower level, in noninflamed mucosae of patients in the remission phase.
CONCLUSIONS: TR cell frequency is differently regulated in mucosal tissues and at the systemic level during the distinct phases of pediatric IBD. The inactive stage of pediatric IBD is characterized by an incomplete normalization of the immune profile, independently of the clinical efficacy of the therapy. The pediatric, early-onset condition may represent a privileged observatory to dissect the immune-mediated pathogenetic mechanisms at the basis of the disease.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
La Scaleia, Raffaella; Department of Experimental Medicine, Sapienza-University of Rome, Italy
Morrone, Stefania; Department of Experimental Medicine, Liver Unit, Sapienza-University of Rome, Italy
Stoppacciaro, Antonella; Department of Clinical and Molecular Medicine, II Medical School, Sapienza-University of Rome, 00189 Rome, Italy
Scarpino, Stefania; Department of Clinical and Molecular Medicine, II Medical School, Sapienza-University of Rome, 00189 Rome, Italy
Antonelli, Manila; Department of Experimental Medicine, Liver Unit, Sapienza-University of Rome, Italy
Bianchi, Elettra ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques ; Department of Experimental Medicine, Liver Unit, Sapienza-University of Rome, Italy
Di Nardo, Giovanni; Department of Pediatrics, Pediatric Gastroenterology, Liver Unit, Sapienza-University of Rome, Italy
Oliva, Salvatore; Department of Pediatrics, Pediatric Gastroenterology, Liver Unit, Sapienza-University of Rome, Italy
Viola, Franca; Department of Pediatrics, Pediatric Gastroenterology, Liver Unit, Sapienza-University of Rome, Italy
Cucchiara, Salvatore; Department of Pediatrics, Pediatric Gastroenterology, Liver Unit, Sapienza-University of Rome, Italy
Santoni, Angela; Department of Experimental Medicine, Liver Unit, Sapienza-University of Rome, Italy
Palmieri, Gabriella; Department of Experimental Medicine, Liver Unit, Sapienza-University of Rome, Italy
Uccini, Stefania; Department of Clinical and Molecular Medicine, II Medical School, Sapienza-University of Rome, 00189 Rome, Italy
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