Dendritic cells (DCs) play a key role in discriminating between commensal microorganisms and potentially harmful pathogens and in maintaining the balance between tolerance and active immunity. The regulatory role of DC is of particular importance in the gut where the immune system lies in intimate contact with the highly antigenic external environment. Intestinal DC constantly survey the luminal microenvironment. They act as sentinels, acquiring antigens in peripheral tissues before migrating to secondary lymphoid organs to activate naive T cells. They are also sensors, responding to a spectrum of environmental cues by extensive differentiation or maturation. Recent studies have begun to elucidate mechanisms for functional specializations of DC in the intestine that may include the involvement of retinoic acid and transforming growth factor-β. Specialized CD103+ intestinal DC can promote the differentiation of Foxp3+ regulatory T cells via a retinoic acid-dependent process. Different DC outcomes are, in part, influenced by their exposure to microbial stimuli. Evidence is also emerging of the close interaction between bacteria, epithelial cells, and DC in the maintenance of intestinal immune homeostasis. Here we review recent advances of functionally specialized intestinal DC and their mechanisms of antigen uptake and recognition. We also discuss the interaction of DC with intestinal microbiota and their ability to orchestrate protective immunity and immune tolerance in the host. Lastly, we describe how DC functions are altered in intestinal inflammation and their emerging potential as a therapeutic target in inflammatory bowel disease. (Inflamm Bowel Dis 2010)
1Antigen Presentation Research Group, Faculty of Medicine, Imperial College London, Northwick Park and St Mark's Campus, Harrow, UK
2St Vincent's Hospital & University of Melbourne, Melbourne, Australia, and Imperial College London, UK
3Centre for Immunology & Infectious Disease, Queen Mary University of London, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, UK
*Reprints: Antigen Presentation Research Group, Imperial College London, Level 7, Northwick Park and St Mark's Hospital campus, Watford Road, Middlesex, HA1 3UJ UK
Received for publication 1 January 2010; Accepted 11 January 2010.
Published online 10 March 2010 in Wiley Online Library (wileyonlinelibrary.com).