Special reports and reviewsGastrointestinal dendritic cells play a role in immunity, tolerance, and disease
Section snippets
DC populations and their location in the gastrointestinal tract
In an attempt to generate a comprehensive review of the current literature relevant to the function of the immune system in the gastrointestinal tract, we focus on studies that have involved DC isolated from the gut, as opposed to those studies of DC from other tissue origins (i.e., spleen and peripheral lymph nodes [PLN]), because it is increasingly evident that the tissue microenvironment, among other factors, can significantly influence DC responses to stimulation.
The phenotypic analysis of
Antigen uptake by DC in the GI tract
The organization of the mucosal immune system has been elegantly reviewed elsewhere5 and can be roughly divided into organized lymphoid tissues (including Peyer’s patches and MLN) and generalized or diffuse tissues interspersed with effector cells of the immune system (lamina propria and intestinal epithelium). Traditionally, Peyer’s patches have been studied as the main site for induction of mucosal immunity, given their intimate localization with the intestinal lumen, the presence of B-cell
Migration of DC in the GI tract
DC migration is an important attribute for the ability of DC to control and disseminate an immune response, and a number of key studies have highlighted the diversity in chemokine responsiveness by different DC populations located in the same intestinal tissues. Because DC migration is thought to be largely under the control of chemokines and chemokine receptors, it is informative to determine chemokine receptor expression and reactivity to chemokines by different GI DC populations in vitro and
GI DC contribution to immunity
Engagement of the members of the TNFR family on DC is a well-published methodology to enhance DC immunostimulatory function. However, DC isolated from GI tissues can exhibit different responses to such stimuli. Engagement of RANK on DC by RANKL that is usually expressed on activated T cells has been shown to stimulate the secretion of cytokines such as IL-1, IL-6, and IL-12 by splenic DCs but appears to induce IL-10 transcription in Peyer’s patch DC.49 It is tempting to speculate, therefore,
GI DC contribution to tolerance
Potential mechanisms underlying tolerance in the GI tract have been thoroughly reviewed elsewhere.54 In this section of the review, we will highlight some of the major points, with particular focus on the role of DC in tolerance under steady-state conditions and tolerance induced following oral administration of protein. The potential mechanisms for oral tolerance induction have included functional T-cell anergy/deletion or induction of regulatory T cells that produce TGF-β (Th3) or IL-10
GI DC contribution to disease
Animal model systems of colitis have been used extensively in an effort to determine the possible mechanisms that contribute to the initiation of colitis in humans.74 One model in particular has been very well characterized and involves the transfer of CD45RB high CD4+ T cells to SCID mice, which leads to the development of chronic colitis with intestinal pathology similar to that seen for IBD in humans.75 Studies focusing on the early events of this model implicated a role for DC in the
Conclusion
When discussing the role of DC and DC subsets in the intestinal immune system, we should make a cautionary note. The influence of a variety of different parameters, including antigen dose; T-cell cross-talk; local cytokine, chemokine, or metabolite production; signals through pathogen interactions; and local tissue microenvironment, just to name a few, are likely to have the ability to influence the outcome of T-cell priming by DC populations. Thus, it is increasingly obvious that we must
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2019, Clinical and Basic Neurogastroenterology and MotilityInsight into the role of TSLP in inflammatory bowel diseases
2017, Autoimmunity ReviewsCitation Excerpt :Activation of STAT5 by TSLP in particular was found to promote development of B and T cells while activating DCs to secrete more chemokines involved in Th2 cell differentiation via upregulation of MHC class I and II molecules in addition to activating mast cells and NKT cells [6,24,25]. Considering their ability to induce Th2 differentiation in in vitro T cell priming assays and stimulate B-cells to secrete immunoglobulin A (IgA), mucosal DCs have long been considered to function as a crucial factor in creating a non-inflammatory environment in the gut [26–28]. More importantly, studies have found that various factors such as TSLP, IL-25 and those expressed by the epithelial cells are key mediators of this process [29].
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2016, Jubb, Kennedy and Palmer's Pathology of Domestic Animals: Sixth EditionTwo wheat decapeptides prevent gliadin-dependent maturation of human dendritic cells
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Dr. Bilsborough’s current address is: Zymogenetics, 1201 Eastlake Avenue E, Seattle, Washington 98102.