Role of mucosal dendritic cells in inflammatory bowel disease

Niess, Jan Hendrik

doi:10.3748/wjg.14.5138

Cited by 74 publications

(52 citation statements)

References 130 publications

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“…It could also result from other relevant factors that have yet to be investigated (e.g. gut dendritic cells, which are immune cells in the mucosa that play a key role in the communication between innate and adaptive immunity 118 ). Immune cell reactivity assays are also necessary for determining whether IBS-related alterations in the gut immune system are qualitative or quantitative.…”

Section: Immune Activation In Ibs Patientsmentioning

confidence: 99%

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

187

180

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This uncommissioned review article was subject to full peer-review. SUMMARY BackgroundIrritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. AimTo determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. MethodsThe scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. ResultsImmune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. ConclusionsThe changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology.

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Section: Immune Activation In Ibs Patientsmentioning

confidence: 99%

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

187

180

View full text Add to dashboard Cite

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“…Dendritic cells (DCs) and macrophages sense luminal antigens and provide signals for induction of tolerance to ingested antigens and commensal bacteria or for initiation of inflammatory immune responses, facilitating activation of adaptive immunity (7,8). Intestinal DCs consist of two functionally distinct subsets based on expression of CD103 and chemokine (C-X3-C motif) receptor 1 (CX3CR1) (9).…”

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confidence: 99%

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4

Kurakevich

Hennet

Hausmann

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Breast milk oligosaccharides shape the intestinal environment by affecting mucosal immunity and bacterial colonization. To clarify the role of milk oligosaccharide sialyl(α2,3)lactose (3SL) in intestinal physiology and disease, we investigated colitis development in Il10 −/− mice exposed to normal or 3SL-deficient milk during lactation. Onset and progression of intestinal inflammation were delayed in Il10 −/− mice deficient for the α2,3 sialyltransferase 4 (ST3GAL4) responsible for 3SL biosynthesis. The proinflammatory role of 3SL was confirmed by showing that oral supplementation of newborn Il10 −/− ;St3gal4 −/− mice with 3SL increased colitis severity. Conversely, fostering of newborn Il10 −/− mice to lactating St3gal4 −/− mothers reduced colitis severity. 3SL directly stimulated mesenteric lymph node CD11c + dendritic cells and induced production of cytokines required for expansion of T H 1 and T H 17 T cells. The stimulatory effect of 3SL was attenuated in Tlr4-deficient CD11c + cells, demonstrating that 3SL induces inflammation through Toll-like receptor 4 (TLR4) signaling. Thus, 3SL directly modulates mucosal immunity, which increases susceptibility to colitis.carbohydrate | glycan | prebiotics | mouse innate immunity I nflammatory bowel disease (IBD) affects up to 0.8% of the Western population and this number is constantly growing worldwide (1). The etiology of IBD is not fully understood, although a number of genetic and environmental factors leading to aberrant mucosal immune responses have been identified (2). Nutrition and especially breastfeeding affects the risk for IBD (3). Breastfeeding for at least 3 mo, accordingly, contributes to a lower incidence for IBD (4); however, these data still are controversial. Oligosaccharides are major constituents of breast milk fulfilling various functions, such as promoting growth of beneficial bacteria, acting as soluble receptors preventing attachment of pathogens in the gastrointestinal tract, and reducing adhesion of leukocytes (4, 5). The exact functions of individual oligosaccharides remain however largely unknown.The limited structural diversity of mouse milk oligosaccharides, including only sialyl(α2,3)lactose (3SL) and sialyl(α2,6)lactose (6SL), enables assessing the specific functional contribution of these oligosaccharides to intestinal homeostasis (6). A recent study provided unique evidence that milk-derived 3SL, but not 6SL, increased susceptibility to dextran sulfate sodium (DSS)-induced acute colitis (6). These findings indicate that individual milk oligosaccharides may not only mediate protective effects, but may promote inflammation as well.Mucosal innate immunity has a pivotal role in regulating inflammatory responses (2). Dendritic cells (DCs) and macrophages sense luminal antigens and provide signals for induction of tolerance to ingested antigens and commensal bacteria or for initiation of inflammatory immune responses, facilitating activation of adaptive immunity (7,8). Intestinal DCs consist of two functionally distinct subsets based on e...

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“…Since IBD is driven partly by overreactive T-cell responses to commensal antigens [2,52], and heightened Th1/17 responses are pathogenic in CD [46,53], our results constitute a significant advance in understanding how the chronic cycle of intestinal inflammation in IBD is maintained.…”

Section: Discussionmentioning

confidence: 99%

ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturation

2012

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Intestinal epithelial cells (IECs) normally promote the development of gut resident tolerogenic dendritic cells (DCs) and regulatory T cells, but how this process is altered in inflam- IntroductionIntestinal epithelial cells (IECs) coordinate the dynamic interactions between luminal microbes and local immune cells and represent the front line of enteric defense [1]. In addition to acting as a physical barrier to prevent passage of luminal contents, Correspondence: Dr. Theodore S. Steiner e-mail: flagellin@gmail.comIECs are crucial for maintaining intestinal homeostasis by sampling the luminal microenvironment, integrating signals received from pattern recognition receptors (PRRs) and local immune cells, and secreting factors that regulate adaptive immunity by priming intestinal dendritic cells (DCs) [2]. Under steady state conditions, IECs maintain a hyporesponsive state to commensal flora by secreting factors such as thymic stromal lymphopoietin (TSLP), TGF-β, and retinoic acid (RA), which together facilitate the development of tolerogenic DCs and regulatory T (Treg) cells [3,4]. During enteric infection, however, TLR-mediated activation of IECs can C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2012. 42: 3310-3321 Immunodulation 3311 initiate robust inflammatory responses. How IECs discriminate between TLR ligands presented by invasive pathogens versus commensal microbes remains largely unknown [5]. One way that IECs may respond to pathogens is by recognizing specific danger signals such as extracellular ATP [6,7]. Recently, several groups reported that ATP contributes to the pathogenesis of a variety of inflammatory disorders, such as asthma, graft versus host disease, and inflammatory bowel disease (IBD), suggesting it is an endogenous danger signal that promotes inflammation [8][9][10][11][12]. Importantly, low expression of CD39, an enzyme that hydrolyzes ATP, is associated with increased risk for Crohn's disease (CD) [12]. Consistent with this finding, CD39-deficient mice have increased susceptibility to dextran sulfate sodium (DSS) induced colitis [12]. The association of ATP with enhanced inflammation in the gut has also lead to the recent identification of commensal bacteria that actively produce ATP in the lumen [13,14], providing another important source of ATP in addition to epithelial injuries as a result of inflammation [14,15]. In the context of IBD, where patients have weaker intestinal barrier function and bacterial leakage across the mucus layer, IECs represent the important first responders to cellular stress and microbial ligands. Therefore, it is essential to understand how ATP regulates inflammatory responses to TLR activation in IECs.Previous work in our laboratory showed that ATP regulates the inflammatory response to flagellin-TLR5 ligation in human IECs and that rectal administration of ATP enhanced flagellinmediated inflammation during DSS-colitis [16]. In this study, we extend our findings to murine IECs and utilize an in vitro coculture mode...

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Role of mucosal dendritic cells in inflammatory bowel disease

Cited by 74 publications

References 130 publications

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4

ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturation

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Role of mucosal dendritic cells in inflammatory bowel disease

Cited by 74 publications

References 130 publications

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c + cells through TLR4

ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturation

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Product

Resources

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Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c ⁺ cells through TLR4