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Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease

Authors

  • Brian L. Kelsall,

    Corresponding author
    1. Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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  • Francisco Leon

    1. Present address: Clinical Discovery-Immunology, Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ, USA.
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† Dr Brian L. Kelsall
Mucosal Immunobiology Section
Laboratory of Molecular Immunology
National Institutes of Allergy and Infectious Diseases
National Institutes of Health
10/11N113
10 Center Drive
Bethesda, MD 20892
USA
Tel.: +1 301 496 7473
Fax: +1 301 480 6768
E-mail: kelsall@nih.gov

Abstract

Summary:  Dendritic cells (DCs) are composed of a family of cells, now recognized to be essential for innate and acquired immunity. DCs at mucosal surfaces have a particular capacity to induce the differentiation of regulatory T cells producing interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the steady state (non-infected, non-immunized), yet they retain the capacity to induce effector T cells in response to invasive pathogens. This decision between the induction of active immunity and tolerance will depend on the subpopulation of DC involved and the surface receptors engaged during DC activation and T-cell priming. The local microenvironment will likely play an important role both in defining the DC phenotype and in providing direct signals to responding T cells. Furthermore, DCs in organized mucosal lymphoid tissues preferentially induce the expression of CCR9 and α4β7 on T cells, which results in T-cell homing to the intestinal lamina propria. Finally, DCs may play an important role in the maintenance of abnormal intestinal inflammation either by driving pathogenic T-cell responses in mesenteric lymph nodes or by acting to expand or maintain pathogenic T cells locally at sites of inflammation. In this review, a brief discussion of general issues of DC biology that are pertinent to mucosal immunity is followed by a more in-depth discussion of the phenotype and function of DC populations in the intestine.

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