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World J Gastroenterol. Sep 7, 2011; 17(33): 3761-3775
Published online Sep 7, 2011. doi: 10.3748/wjg.v17.i33.3761
Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease
Sergio Rutella, Franco Locatelli
Sergio Rutella, Franco Locatelli, Department of Pediatric Hematology/Oncology, IRCCS Children’s Hospital “Bambino Gesù”, 00165 Rome, Italy
Sergio Rutella, Catholic University Medical School, 00168 Rome, Italy
Franco Locatelli, University of Pavia, 27100 Pavia, Italy
Author contributions: Rutella S wrote the manuscript draft; Locatelli F gave intellectual input and advice, and contributed to manuscript writing.
Supported by The “Stem Cell Project”, Fondazione Roma, Italy and by the Associazione Italiana per la Ricerca sul Cancro, Milan, Italy (AIRC, Grant No. 8556)
Correspondence to: Dr. Sergio Rutella, MD, PhD, Department of Pediatric Hematology/Oncology, IRCCS Children's Hospital "Bambino Gesù", Piazza Sant'Onofrio 4, 00165 Rome, Italy. sergio.rutella@opbg.net
Telephone: +39-66-8592678 Fax: +39-66-8592292
Received: October 21, 2010
Revised: January 18, 2011
Accepted: January 25, 2011
Published online: September 7, 2011

The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens. For these reasons, the intestinal immune system is uniquely dedicated to protect against infections, while avoiding the development of destructive inflammatory responses to the microbiota. Several models have been proposed to explain how the immune system discriminates between, and appropriately responds to, commensal and pathogenic microorganisms. Dendritic cells (DCs) and regulatory T cells (Treg) are instrumental in maintaining immune homeostasis and tolerance in the gut. DCs are virtually omnipresent and are remarkably plastic, having the ability to adapt to the influences of the microenvironment. Different DC populations with partially overlapping phenotypic and functional properties have been described in different anatomical locations. DCs in the draining mesenteric lymph nodes, in the intestinal lamina propria and in Peyer’s patches partake both in the control of intestinal inflammation and in the maintenance of gut tolerance. In this respect, gut-resident DCs and macrophages exert tolerogenic functions as they regularly encounter and sense commensal bacteria. In contrast, migrating DC subsets that are recruited to the gut as a result of pathogenic insults initiate immune responses. Importantly, tolerogenic DCs act by promoting the differentiation and expansion of Treg cells that efficiently modulate gut inflammation, as shown both in pre-clinical models of colitis and in patients with inflammatory bowel disease (IBD). This article reviews the phenotypic and functional features of gut DC subsets and discusses the current evidence underpinning the DC contribution to the pathogenesis of the major clinical subtypes of human IBD. It also addresses the potential clinical benefit derived from DC targeting either in vivo or in vitro.

Keywords: Dendritic cell, Tolerance, Gut, Inflammatory bowel disease, Cytokine, Regulatory T cells