Interactions among dendritic cells, macrophages, and epithelial cells in the gut: implications for immune tolerance

Rescigno, María; Lopatin, Uri; Chieppa, Marcello

doi:10.1016/j.coi.2008.09.007

Cited by 94 publications

(81 citation statements)

References 53 publications

(51 reference statements)

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“…Therefore, intestinal ECs trigger inflammatory responses to activate T cell development via ATP sensing. Indeed, intestinal ECs were shown to control DC functions (47).…”

Section: Discussionmentioning

confidence: 99%

Ecto-Nucleoside Triphosphate Diphosphohydrolase 7 Controls Th17 Cell Responses through Regulation of Luminal ATP in the Small Intestine

Kusu

Kayama

Kinoshita

et al. 2013

The Journal of Immunology

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Extracellular ATP is released from live cells in controlled conditions, as well as dying cells in inflammatory conditions, and, thereby, regulates T cell responses, including Th17 cell induction. The level of extracellular ATP is closely regulated by ATP hydrolyzing enzymes, such as ecto-nucleoside triphosphate diphosphohydrolases (ENTPDases). ENTPDase1/CD39, which is expressed in immune cells, was shown to regulate immune responses by downregulating the ATP level. In this study, we analyzed the immunomodulatory function of ENTPDase7, which is preferentially expressed in epithelial cells in the small intestine. The targeted deletion of Entpd7 encoding ENTPDase7 in mice resulted in increased ATP levels in the small intestinal lumen. The number of Th17 cells was selectively increased in the small intestinal lamina propria in Entpd7−/− mice. Th17 cells were decreased by oral administration of antibiotics or the ATP antagonist in Entpd7−/− mice, indicating that commensal microbiota-dependent ATP release mediates the enhanced Th17 cell development in the small intestinal lamina propria of Entpd7−/− mice. In accordance with the increased number of small intestinal Th17 cells, Entpd7−/− mice were resistant to oral infection with Citrobacter rodentium. Entpd7−/− mice suffered from severe experimental autoimmune encephalomyelitis, which was associated with increased numbers of CD4+ T cells producing both IL-17 and IFN-γ. Taken together, these findings demonstrate that ENTPDase7 controls the luminal ATP level and, thereby, regulates Th17 cell development in the small intestine.

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“…Therefore, intestinal ECs trigger inflammatory responses to activate T cell development via ATP sensing. Indeed, intestinal ECs were shown to control DC functions (47).…”

Section: Discussionmentioning

confidence: 99%

Ecto-Nucleoside Triphosphate Diphosphohydrolase 7 Controls Th17 Cell Responses through Regulation of Luminal ATP in the Small Intestine

Kusu

Kayama

Kinoshita

et al. 2013

The Journal of Immunology

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“…It is beyond the scope of the present review to consider in detail the various aspects of tolerance, particularly the complexities involved with tolerance at mucosal surfaces. For more detailed information on this area, the reader is recommended to future science group read the numerous reviews already published on tolerance [24,27,[29][30][31][32][33]. The remainder of this subsection will highlight certain elements that are particularly pertinent when designing delivery to mucosal DCs for the induction of local immunity or tolerance (as in the case of an inflammatory disorder such as inflammatory bowel disease).…”

Section: Processing Antigen For Presentation To Tc-lymphocytesmentioning

confidence: 99%

Functional RNA Delivery Targeted to Dendritic Cells By Synthetic Nanoparticles

McCullough¹,

Bassi²,

Démoulins³

et al. 2012

Therapeutic Delivery

102

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ReviewTargeting the immune system Dendritic cells (DCs) play crucial roles in promoting and regulating immune defenses, providing important targets for prophylactic and therapeutic approaches (FiguRe 1). Particulate formulations, including liposomes and other nanoparticles, have been employed as delivery vehicles. Despite the large number of reports, current in-depth knowledge on the cellular processes involved remains relatively limited, particularly for nucleic acid delivery. Certain structures in the nucleic acid may also signal the cell in the sense of an adjuvant or immunomodulatory activity. Importantly, the optimized characteristics for delivery of an antigen or therapeutic agent may be distinct from those for nucleic acid delivery, especially RNA species. Moreover, RNA delivery for interference therapy will not necessarily require the same delivery routes as mRNA delivery wherein RNA translation is the main requisite.The efficacy of delivery can be further improved by targeting the appropriate cells of the immune system, an area in which nanoparticle-based delivery platforms have found an important niche [1]. Advances with prophylactic applications can also prove valuable for therapeutic applications and vice versa, as seen with RNA delivery. This review will consider how growing knowledge on delivery mechanisms has found application with nucleic acids, in both prophylaxis and therapy, focusing on interaction with DCs.The initial components of the DC endocytic pathways are critically important in determining how the cell handles the delivered material; thereafter, correct cytosolic delivery is a critical element for a number of desired outcomes, including delivery of nucleic acids. Advances made with protein delivery -in particular, vaccines -are of value to highlight the potential of a particular mode of application or the high risk for nucleic acid integrity. Particularly pertinent is the application of cationic elements in the delivery mechanisms and how application of ligands for cell receptors influence intracellular compartmentalization.It is not the aim of the present review to retrace all the fine details of work contributing to our current knowledge. Accordingly, review articles covering areas that have already received considerable attention will be employed and assimilated to provide a more elaborate picture of the current situation. This will allow a focusing on more recent advances, along with problems and pitfalls therein. While advances on protein and DNA delivery will be presented, these will be used to highlight how our current knowledge can be applied to RNA delivery. There are numerous reviews on protein delivery to DC, wherein many of the procedures employed are not relevant for RNA delivery, which must escape into the cytosol undamaged. With DNA delivery, there is also the question of whether the DNA will activate the DC or reach the nucleus for transcription; this latter area has most often Functional RNA delivery targeted to dendritic cells by synthetic nanoparticles Dendritic cell...

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“…Cytokines or chemokines are produced by IEC in response to potentially harmful substances, which are detected by a battery of pathogenrecognition receptors. These receptors are involved in the regulation of physiological and pathophysiological processes of the intestinal mucosa, including immunity and inflammation, via activation of MAPK and the key transcription factor, NF-kB [1][2][3][4]. The first widely studied family of receptors was the TLR family.…”

Section: Introductionmentioning

confidence: 99%

“…The first widely studied family of receptors was the TLR family. Eleven mammalian TLR have been identified, of which TLR1-6 and TLR9 are expressed in IEC [3][4][5]. Another group of pathogenrecognition receptors, termed nucleotide-binding and oligomerisation domain (NOD) proteins, provide a second line of innate immune defence against bacterial infection.…”

Section: Introductionmentioning

confidence: 99%

Butyrate mediates nucleotide‐binding and oligomerisation domain (NOD) 2‐dependent mucosal immune responses against peptidoglycan

Leung

Lam

et al. 2009

Eur J Immunol

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The interaction between digestive tract microbiological flora and food has an important influence on human health. Butyrate is produced during the fermentation of dietary fibres by intestinal bacteria and plays an important role in the regulation of mucosal immunity. In this report, we studied the impact of butyrate on the defence mechanism against the bacterial membrane component peptidoglycan (PGN). Butyrate was found to enhance PGN-mediated IL-8 and GRO-a production. The expression of these chemokines required the activation of NF-jB and was dependent on the concentrations of butyrate and PGN. Butyrate was found to up-regulate nucleotide-binding and oligomerisation domain (NOD) 2, but not NOD1 or TLR2. NOD2 up-regulation was mediated by an increase in histone acetylation in the Nod2 promoter region, leading to enhanced PGN-induced IL-8 and GRO-a secretion. Knockdown of NOD2 and TLR2 by siRNA significantly reduced PGNmediated chemokine production, suggesting that both NOD2 and TLR2 are required for maximal response. Our findings provide a better understanding of the mechanism by which butyrate regulates mucosal immunity for normal intestinal function. Based on the results of this study, we infer that dietary fibres can impact inflammatory bowel diseases.Key words: Butyrate . Intestinal immunity . Nucleotide-binding and oligomerization domains (NOD) .Peptidoglycan . TLR IntroductionIntestinal epithelial cells (IEC) function as a physical barrier against foreign substances in the intestinal lumen, such as food and pathogenic and non-pathogenic microorganisms. These cells are also involved in the host immune defence. Cytokines or chemokines are produced by IEC in response to potentially harmful substances, which are detected by a battery of pathogenrecognition receptors. These receptors are involved in the regulation of physiological and pathophysiological processes of the intestinal mucosa, including immunity and inflammation, via activation of MAPK and the key transcription factor, NF-kB [1][2][3][4]. The first widely studied family of receptors was the TLR family. Eleven mammalian TLR have been identified, of which TLR1-6 and TLR9 are expressed in IEC [3][4][5]. Another group of pathogenrecognition receptors, termed nucleotide-binding and oligomerisation domain (NOD) proteins, provide a second line of innate immune defence against bacterial infection. This family consists of more than 20 members and is located primarily in the cytosol. While NOD1 is constitutively expressed in IEC, the level of NOD2 expression is very low [1,2]. The bi-directional interaction between digestive tract microbiological flora and food has an important influence on human health, particularly on the immune response [6,7]. Butyrate is There is an increasing body of evidence demonstrating the importance of butyrate in maintaining intestinal mucosal immunity [9][10][11]. Butyrate has been shown to switch the transcriptional pattern of chemokine production through promotion of histone acetylation [12]. Several studies have also suggested...

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Interactions among dendritic cells, macrophages, and epithelial cells in the gut: implications for immune tolerance

Cited by 94 publications

References 53 publications

Ecto-Nucleoside Triphosphate Diphosphohydrolase 7 Controls Th17 Cell Responses through Regulation of Luminal ATP in the Small Intestine

Ecto-Nucleoside Triphosphate Diphosphohydrolase 7 Controls Th17 Cell Responses through Regulation of Luminal ATP in the Small Intestine

Functional RNA Delivery Targeted to Dendritic Cells By Synthetic Nanoparticles

Butyrate mediates nucleotide‐binding and oligomerisation domain (NOD) 2‐dependent mucosal immune responses against peptidoglycan

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