Characteristics of Intestinal Dendritic Cells in Inflammatory Bowel Diseases (original) (raw)
2018
Background Dendritic cells play crucial roles in the control of inflammation and immune tolerance in the gut. We aimed to investigate the effects of tumor necrosis factor alpha (TNFa) inhibitors on intestinal dendritic cells in patients with inflammatory bowel disease and the potential role of intestinal dendritic cells in predicting the response to treatment. Patients and methods Intestinal biopsies were obtained from 30 patients with inflammatory bowel disease before and after treatment with TNFa inhibitors. The proportions of lamina propria dendritic cell phenotypes were analysed using flow cytometry. Disease activity was endoscopically assessed at baseline and after the induction treatment. Results At baseline, the proportion of conventional dendritic cells was higher in the inflamed mucosa (7.8%) compared to the uninflamed mucosa (4.5%) (p = 0.003), and the proportion of CD103+ dendritic cells was lower in the inflamed mucosa (47.1%) versus the uninflamed mucosa (57.3%) (p = 0....
European Journal of Gastroenterology & Hepatology, 2001
Objective Increased lymphocyte activation and production of in¯ammatory cytokines are implicated in the pathogenesis of ulcerative colitis. Because antigenpresenting dendritic cells play a cardinal role in the activation and survival of activated lymphocytes, the aim of the present study was to characterize dendritic cells in ulcerative colitis. Design This study was designed to compare the phenotypes and functions of peripheral blood dendritic cells among healthy normal volunteers and patients with ulcerative colitis or Crohn's disease. Activated dendritic cells were also localized at the colonic mucosa. Methods Peripheral blood dendritic cells were generated from 15 patients with ulcerative colitis, 10 patients with Crohn's disease and 15 healthy control volunteers. The stimulatory capacities of dendritic cells were analysed in an allogenic mixed lymphocyte reaction. Nitric oxide was detected by the Griess method. Single-and dual-colour ow cytometry was employed to study the levels of maturation of dendritic cells. Activated dendritic cells were localized immunohistochemically in the colonic mucosa. Results In comparison to normal controls, peripheral blood dendritic cells from patients with ulcerative colitis showed signi®cantly increased stimulatory capacities (P < 0.05) and produced signi®cantly higher levels of nitric oxide (P < 0.05). The numbers of activated dendritic cells were also signi®cantly higher in ulcerative colitis (P < 0.05). Mature and activated dendritic cells expressing the CD83 antigen were detected at the in¯amed colonic mucosa in patients with ulcerative colitis and Crohn's disease. Conclusions Activated and mature dendritic cells may have a role in the induction of an exacerbated immune response in ulcerative colitis. This study provides the scienti®c and logical basis for blocking the maturation and activation of dendritic cells in ulcerative colitis as a new therapeutic intervention.
Inflammatory Bowel …, 2004
Ulcerative colitis and Crohn's disease, collectively termed inflammatory bowel diseases (IBD), are chronic inflammatory diseases of the intestine that afflict more than 4 million people worldwide. Intestinal inflammation is characterized by an abnormal mucosal immune response to normally harmless antigens in the gut flora. In Crohn's disease, the pathogenic mucosal immune response is a typical T helper (T H 1) type cell response, whereas ulcerative colitis is predominantly associated with a T H 2 response. We are interested in the role of dendritic cells in early immunologic events leading to T cell activation and chronic intestinal inflammation. Using a murine adoptive transfer model of IBD, we found an accumulation of dendritic cells in colon and mesenteric lymph nodes during the early stage of IBD before the appearance of epithelial lesions and tissue degradation. In situ immunostaining and flow-cytometric analysis revealed that approximately 50% of colonic dendritic cells were CD11b + B220 − myeloid dendritic cells and 50% expressed the CD11b − B220 + plasmacytoid phenotype. In corresponding mesenteric lymph nodes, approximately 16% were plasmacytoid dendritic cells. Colonic myeloid dendritic cells were shown to express the co-stimulatory molecule CD40. Both, colonic myeloid and plasmacytoid dendritic cells released interferon-␣ in situ and stimulated T cell proliferation ex vivo. Our results show that dendritic cells can mature in the intestine without migrating to mesenteric lymph nodes. Mature intestinal dendritic cells may form a nucleation site for a local T cell response and play an important role in the pathogenesis of IBD.
Characterization and Distribution of Colonic Dendritic Cells in Crohn’s Disease
Inflammatory Bowel Diseases, 2004
Dendritic cells (DCs) are thought to play an important role in the pathogenesis of autoimmune inflammation, including Crohn's disease (CD). We investigated the distribution and state of maturation of DCs in the colon in relation to the severity of inflammation and therapy. Using archival specimens from colonic resections in 19 pediatric patients with CD and 14 controls, we identified and characterized the DCs within the lamina propria, submucosa, and muscularis compartments using morphologic and quantitative immunohistochemical methods. The distribution of CD11c + CD83 + CD68 − DC-SIGN + and immature CD11c + CD83 − CD68 − DC-SIGN + DCs within the different compartments varied according to the presence or absence of CD as well as to the severity of inflammation and systemic corticoid treatment. Immature DCs were only found in non-inflamed control colonic tissue. Marked reductions (60% and 30%) in total CD11c + and CD83 + DC numbers were observed in CD tissue samples compared with controls (P < 0.05). CD samples from patients on corticosteroid therapy were significantly more depleted than in tissue from untreated patients or those on other drugs. Colonic tissue with severe inflammation had reduced numbers of CD11c + and CD83 + DCs in the lamina propria and submucosal compartments (80% and 76% for CD11c; 75% and 76% for CD83, respectively, P < 0.05), with a concomitant increase (525% for CD11c and 700% for CD83 P < 0.05) of DCs in the muscularis compartment, compared to moderately inflamed and non-inflamed CD tissue. Our data suggest that an imbalance in intestinal DC subpopulations may play a role in the initiation and/or the maintenance of chronic inflammation in CD. Corticosteroid therapy is associated with colonic DC depletion.
Characterization of colonic dendritic cells in normal and colitic mice
World journal of gastroenterology : WJG, 2005
Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2(-/-)) mice that develop colitis. In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c(+), CD11b(+), B220(-), CD8alpha(-)) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40, and had high endocytic activity consistent with an immature phenotype. In colitic IL2(-/-) mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within agg...
Current Opinion in Gastroenterology, 2015
Purpose of review The intestinal immune system is constantly exposed to foreign antigens, which for the most part should be tolerated, but the immune system retains the ability to react rapidly and effectively to eliminate pathogens. Dendritic cells are at the front line in maintaining intestinal integrity as they are widely distributed within the intestinal lamina propria, Peyer's patches and mesenteric lymph nodes.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2010
Disturbed immunoregulation and an inappropriate immune response to gut microflora is assumed to be involved in the pathogenesis of inflammatory bowel disease (IBD). Physiologically dendritic cells (DCs) as the professional antigen presenting cells play a crucial role in the control of intestinal inflammation and immune tolerance. In order to evaluate their role in the IBD we analyzed the phenotypic and functional properties of monocyte-derived DCs (MoDCs) generated from UC and CD patients following stimulation with TNF-α, lipopolisaccharide E. coli or hydrocortisone. Thirty seven patients with moderate to severe inflammation (19 UC, 18 CD) were recruited to the study. Monocyte-derived dendritic cell immunophenotypes and their endocytic ability were analysed by flow cytometry and confocal microscopy, IL-6, IL-10, IL-12 and IL-23 secretion were investigated by ELISA. Both unstimulated and stimulated MoDCs generated from IBD patients had more mature phenotype and secreted elevated conc...
Immunology Letters, 2013
The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota and food antigens. Dendritic cells (DC) generate primary T-cell responses, and determine whether these responses are immunogenic or tolerogenic. The regulatory role of DC is of particular importance in the gut due to the high antigenic load. Intestinal DC act as sentinels, sampling potentially pathogenic antigens but also harmless antigens including the commensal microbiota. Following antigen acquisition, intestinal DC migrate to secondary lymphoid organs to activate naive T-cells. DC also imprint specific homing properties on T-cells that they stimulate; gut DC specifically induce gut-homing properties on T-cells upon activation, enabling T-cell migration back to intestinal sites. Data regarding properties on gut DC in humans is scarce, although evidence now supports the role of DC as important players in intestinal immunity in humans. Here, we review the role of intestinal DC in shaping mucosal immune responses and directing tissue-specific T-cell responses, with a special focus on the importance of distinguishing DC subsets from macrophages at intestinal sites. We compare and contrast human DC with their murine counterparts, and discuss the ability of the gut microbiota to shape intestinal DC function, and how this may be dysregulated in inflammatory bowel disease (IBD). Lastly, we describe recent advances in the study of probiotics on intestinal DC function, including the use of soluble secreted bacterial products.
Inflammatory Bowel Diseases, 2006
We examined ileal dendritic cell (DC) subpopulations in a rat model of indomethacin-induced enteritis to determine changes in phenotype and distribution associated with increased mucosal permeability during acute and chronic stages of inflammation. Sprague-Dawley rats were treated with indomethacin (7.5 mg/kg subcutaneously, 2 injections 48 h apart). Animals were killed at day 4 (acute stage) or at day 15 or 30 (chronic stages); control rats were injected with saline. DC distribution was evaluated by immunohistochemistry for CD103, CD11b, CD83, and CD163; inflammation was assessed by light microscopy; and permeability was determined by flux of horseradish peroxidase in Ussing chambers. In controls, both immature DC subpopulations, CD103 + CD11b + CD163 j CD83 j and CD103 + CD11b j CD163 j CD83 j , were observed in the lamina propria, and the CD11b j population also was present in Peyer`s patches. In acute inflammation, permeability was increased (P G 0.01), and inflamed areas with or without ulcers were observed. CD103 + and CD11b + (CD83 j ) DCs were absent from inflamed areas, reduced in noninflamed tissues, but present in Peyer`s patches. In the chronic stage at day 15, CD103 + and CD11b + cells were located in inflamed and noninflamed areas and in Peyer`s patches. In addition, CD83 + DCs were detected in inflamed areas. At day 30, when we observed a complete microscopic resolution of inflammation, numbers of CD103 + and CD11b + DCs were increased, and there were CD83 + DCs beneath the epithelial cell layer. We conclude that antigen uptake in acute inflammation may activate resident immature DCs, inducing their migration to lymphoid tissue where they mature and then return to the intestine to play a role in the local inflammatory response.
Dendritic Cells and Toll-Like Receptors 2 and 4 in the Ileum of Crohn's Disease Patients
Digestive Diseases and Sciences, 2008
We investigated myeloid-dendritic cell (DC) marker and Toll-like receptor (TLR)-2 and 4 distributions in ileal samples from Crohn's disease (CD) patients (n = 14) and controls (n = 13). In controls, no TLR-2 + cells were observed, and higher numbers of TLR-4 + and DC-SIGN + cells (P \ 0.01) were detected in ileal samples when compared versus colonic tissues. In non-inflamed CD ileum, TLR-4 + and DC-SGN + cells were depleted from superficial areas of the villus, and a significant CD1a + cell infiltration (P \ 0.01) was observed when compared to ileal controls and non-inflamed colonic CD samples. In inflamed CD ileum, DC-SIGN + , CD1a + , TLR-4 + and few TLR-4 + DC-SIGN + cells were detected as well as CD83 depletion. No correlation between TLR-2 and DC markers was detected in CD samples. A unique distribution of myeloid-DC markers characterized the CD ileum. Also, the presence of significant amounts of ileal CD1a + cells may provide a relevant DC-mediated mechanism for antigen recognition in the pathogenesis of CD.