Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease

Sergio Rutella, Franco Locatelli

Research output: Contribution to journalArticlepeer-review

Abstract

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 micro-biota. 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.

Original languageEnglish
Pages (from-to)3761-3775
Number of pages15
JournalWorld Journal of Gastroenterology
Volume17
Issue number33
DOIs
Publication statusPublished - Sep 7 2011

Keywords

  • Cytokine
  • Dendritic cell
  • Gut
  • Inflammatory bowel disease
  • Regulatory t cells
  • Tolerance

ASJC Scopus subject areas

  • Gastroenterology

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