scholarly journals When Insult Is Added to Injury: Cross Talk between ILCs and Intestinal Epithelium in IBD

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Esmé van der Gracht ◽  
Sonja Zahner ◽  
Mitchell Kronenberg
Keyword(s):  
Intestinal Epithelium ◽  
Immune Cells ◽  
Intestinal Barrier ◽  
Biochemical Properties ◽  
The Body ◽  
Lymphoid Cells ◽  
Intestinal Lumen ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Critical Feedback

Inflammatory bowel disease (IBD) is characterized by an impairment of the integrity of the mucosal epithelial barrier, which causes exacerbated inflammation of the intestine. The intestinal barrier is formed by different specialized epithelial cells, which separate the intestinal lumen from the lamina propria. In addition to its crucial role in protecting the body from invading pathogens, the intestinal epithelium contributes to intestinal homeostasis by its biochemical properties and communication to underlying immune cells. Innate lymphoid cells (ILCs) are a recently described population of lymphocytes that have been implicated in both mucosal homeostasis and inflammation. Recent findings indicate a critical feedback loop in which damaged epithelium activates these innate immune cells to restore epithelial barrier function. This review will focus on the signalling pathways between damaged epithelium and ILCs involved in repair of the epithelial barrier and tissue homeostasis and the relationship of these processes with the control of IBD.

scholarly journals Protein kinase p38α signaling in dendritic cells regulates colon inflammation and tumorigenesis

2018 ◽  
Vol 115 (52) ◽  
pp. E12313-E12322 ◽  
Author(s):  
Tingting Zheng ◽  
Baohua Zhang ◽  
Ce Chen ◽  
Jingyu Ma ◽  
Deyun Meng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymphoid Cells ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Colon Inflammation ◽  
Effective Immune Response ◽  
Direct Binding ◽  
Group 3 ◽  
Tr1 Cells

Dendritic cells (DCs) play pivotal roles in maintaining intestinal homeostasis, but how the DCs regulate diverse immune networks on homeostasis breakdown remains largely unknown. Here, we report that, in response to epithelial barrier disruption, colonic DCs regulate the differentiation of type 1 regulatory T (Tr1) cells through p38α-dependent IL-27 production to initiate an effective immune response. Deletion of p38α in DCs, but not in T cells, led to increased Tr1 and protected mice from dextran sodium sulfate-induced acute colitis and chronic colitis-associated colorectal cancer. We show that higher levels of IL-27 in p38α-deficient colonic cDC1s, but not cDC2s, were responsible for the increase of Tr1 cells. Moreover, p38α-dependent IL-27 enhanced IL-22 secretion from intestinal group 3 innate lymphoid cells and protected epithelial barrier function. In p38α-deficient DCs, the TAK1–MKK4/7–JNK–c-Jun axis was hyperactivated, leading to high IL-27 levels, and inhibition of the JNK–c-Jun axis suppressed IL-27 expression. ChIP assay revealed direct binding of c-Jun to the promoter of Il27p28, which was further enhanced in p38α-deficient DCs. In summary, here we identify a key role for p38α signaling in DCs in regulating intestinal inflammatory response and tumorigenesis, and our finding may provide targets for the treatment of inflammatory intestinal diseases.

scholarly journals Change of Intestinal Microbiome in Patients with Coronavirus Infection

2021 ◽  
Vol 6 (5) ◽  
pp. 22-27
Author(s):  
M. M. Mishina ◽  
◽  
O. V. Kotsar ◽  
Pochernina M. H. ◽  
O. V. Kochnieva ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Intestinal Barrier ◽  
Multiple Organ ◽  
Infection Process ◽  
The Body ◽  
Intestinal Microbiome ◽  
Intestinal Lumen ◽  
Treatment Regimens ◽  
Analysis And Synthesis ◽  
Coronavirus Infection

The purpose of the study was to analyze modern literature on the problems of dysbiosis in patients with COVID-19, to study the main mechanisms of systemic interaction between the intestine and lungs, as well as changes in the microbiota that occur under the influence of coronavirus infection. Materials and methods. A comprehensive selection of research methods was used for the work: systematization of the material, the method of generalization, methods of analysis and synthesis. Scientific works in the field of microbiology, epidemiology and infectious diseases were studied. Literature data for the last 2 years (2019-2021) were considered. The results of bacteriological studies from patients with COVID infection were described. The data obtained were processed using information-analytical and statistical-analytical methods. Results and discussion. As a result of this work, a complex of connections between intestine and lungs, which is called the "intestinal-lung axis", was considered. It is known that the interaction between these two biotopes occurs with the participation of microflora and its metabolites. Dysfunction of the intestinal barrier is accompanied by bacterial translocation. Bacteria from the intestinal lumen enter the liver through the portal vein system. The lymphatic pathway of bacterial translocation from the intestine to the lungs is also possible, which causes multiple organ failure syndrome in coronavirus infection. The COVID-19 virus is able to reduce the number of ACE2 receptors in the gastrointestinal tract, which leads to an imbalance in the intestines. At the same time, the infection process in the lungs promotes the growth of bacteria of the Enterobacteriacae family in the intestine, which also leads to dysbiotic disorders. The use of probiotics is an effective tool in the complex treatment of this infection, which facilitates the general condition of patients. In the course of treatment, it is important not only to eliminate the virus from the body, but also to restore normal intestinal microbiota after an infection. Conclusion. Thus, the use of probiotic drugs for the treatment of patients with coronavirus infection can significantly reduce the risk of developing dysbiosis and improve the condition of patients. A perspective direction is the development of new treatment regimens for dysbiotic conditions using probiotics, eubiotics, synbiotics and postbiotics to prevent the development of severe complications in COVID infection

scholarly journals A Micro-engineered Human Colon Intestine-Chip Platform to Study Leaky Barrier

2020 ◽  
Author(s):  
Athanasia Apostolou ◽  
Rohit A. Panchakshari ◽  
Antara Banerjee ◽  
Dimitris V. Manatakis ◽  
Maria D. Paraskevopoulou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Unmet Need ◽  
Intestinal Barrier ◽  
Human Colon ◽  
Epithelial Barrier ◽  
Host Immune System ◽  
Intestinal Epithelial ◽  
Barrier Disruption ◽  
Interleukin 22

ABSTRACTThe intestinal epithelial barrier supports the symbiotic relationship between the microbiota colonizing the intestinal epithelium and the host immune system to maintain homeostasis. Leaky barrier is increasingly recognized as part of the pathogenesis of a number of chronic conditions in addition to inflammatory and infectious diseases. As our understanding on the regulation of the barrier remains limited, effective therapeutic targeting for the compromised barrier is still an unmet need. Here we combined advancements on the organoids and Organ-on-Chip technologies to establish a micro-engineered Colon Intestine-Chip for studying development and regulation of the human intestinal barrier. Our data demonstrate the significance of the endothelium in co-culture with the epithelial cells within a tissue-relevant microenvironment for the establishment of a tight epithelial barrier of polarized cells. Pathway analysis of the RNA sequencing (RNA-Seq), revealed significant upregulation of mechanisms relevant to the maturation of the intestinal epithelium in organoid-derived epithelial cells in co-culture with endothelium as compared to organoids maintained in suspension. We provide evidence that the Colon Intestine-Chip platform responds to interferon gamma (IFNγ), a prototype cytokine utilized to model inflammation-induced barrier disruption, by induction of apoptosis and reorganization of the apical junctional complexes as shown with other systems. We also describe the mechanism of action of interleukin 22 (IL-22) on mature, organoid-derived intestinal epithelial cells that is consistent with barrier disruption. Overall we propose the Colon Intestine-Chip as a promising human organoid-derived platform to decipher mechanisms driving the development of leaky gut in patients and enable their translation for this unmet medical need.

scholarly journals Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function

Pharmacology ◽  
2019 ◽  
Vol 105 (1-2) ◽  
pp. 102-108 ◽  
Author(s):  
Norio Nishii ◽  
Tadayuki Oshima ◽  
Min Li ◽  
Hirotsugu Eda ◽  
Kumiko Nakamura ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Fluorescein Isothiocyanate ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Epithelial Permeability ◽  
Epithelial Barrier Function ◽  
Dose Dependent

Introduction: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. Methods: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1β) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. Results: IFNγ, IL-6, IL-1β, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1β, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. Conclusion: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.

scholarly journals 3343 Identification of host-microbial interaction networks that mediate intestinal epithelial barrier function in necrotizing enterocolitis

2019 ◽  
Vol 3 (s1) ◽  
pp. 13-13
Author(s):  
David R Hill ◽  
Roberto Cieza ◽  
Veda K. Yadagiri ◽  
Phillip Tarr ◽  
Jason R. Spence ◽  
...  
Keyword(s):  
Barrier Function ◽  
Bacterial Colonization ◽  
Intestinal Barrier ◽  
Microbial Interactions ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Epithelial Barrier Function ◽  
Novel Approach ◽  
Species Specific

OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.

scholarly journals Long noncoding RNAs in intestinal epithelium homeostasis

2019 ◽  
Vol 317 (1) ◽  
pp. C93-C100 ◽  
Author(s):  
Lan Xiao ◽  
Myriam Gorospe ◽  
Jian-Ying Wang
Keyword(s):  
Intestinal Epithelium ◽  
Rna Binding ◽  
Noncoding Rnas ◽  
The Body ◽  
Long Noncoding Rnas ◽  
Biological Functions ◽  
Mucosal Regeneration ◽  
Epithelial Barrier Function ◽  
Epithelial Homeostasis ◽  
Stressful Environments

The epithelium of the mammalian intestinal mucosa is a rapidly self-renewing tissue in the body, and its homeostasis is preserved through well-controlled mechanisms. Long noncoding RNAs (lncRNAs) regulate a variety of biological functions and are intimately involved in the pathogenesis of diverse human diseases. Here we highlight the roles of several lncRNAs expressed in the intestinal epithelium, including uc.173, SPRY4-IT1, H19, and Gata6, in maintaining the integrity of the intestinal epithelium, focusing on the emerging evidence of lncRNAs in the regulation of intestinal mucosal regeneration and epithelial barrier function. We also discuss recent results that the interactions between lncRNAs with microRNAs and the RNA-binding protein HuR influence epithelial homeostasis. With rapidly advancing knowledge of lncRNAs, there is also growing recognition that lncRNAs in the intestinal epithelium might be promising therapeutic targets in our efforts to protect the integrity of the intestinal epithelium in response to stressful environments.

scholarly journals Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin

2011 ◽  
Vol 208 (11) ◽  
pp. 2263-2277 ◽  
Author(s):  
Georgios Nikitas ◽  
Chantal Deschamps ◽  
Olivier Disson ◽  
Théodora Niault ◽  
Pascale Cossart ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Intestinal Epithelium ◽  
Foodborne Pathogen ◽  
Intestinal Barrier ◽  
Systemic Infection ◽  
Surface Protein ◽  
Intestinal Lumen ◽  
Specific Host ◽  
Species Specific ◽  
E Cadherin

Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection.

scholarly journals CUGBP1 and HuR regulate E-cadherin translation by altering recruitment of E-cadherin mRNA to processing bodies and modulate epithelial barrier function

2016 ◽  
Vol 310 (1) ◽  
pp. C54-C65 ◽  
Author(s):  
Ting-Xi Yu ◽  
Bei-Lin Gu ◽  
Jun-Kai Yan ◽  
Jie Zhu ◽  
Wei-Hui Yan ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Intestinal Barrier ◽  
Primary Component ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Processing Bodies ◽  
Epithelial Barrier Function ◽  
Epithelial Barrier Dysfunction ◽  
E Cadherin

The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs. Here, we present evidence that CUGBP1 and HuR interact directly with the 3′-untranslated region of E-cadherin mRNA and regulate E-cadherin translation. CUGBP1 overexpression in Caco-2 cells inhibited E-cadherin translation by increasing the recruitment of E-cadherin mRNA to processing bodies (PBs), thus resulting in an increase in paracellular permeability. Overexpression of HuR exhibited an opposite effect on E-cadherin expression by preventing the translocation of E-cadherin mRNA to PBs and therefore prevented CUGBP1-induced repression of E-cadherin expression. Elevation of HuR also abolished the CUGBP1-induced epithelial barrier dysfunction. These findings indicate that CUGBP1 and HuR negate each other's effects in regulating E-cadherin translation by altering the recruitment of E-cadherin mRNA to PBs and play an important role in the regulation of intestinal barrier integrity under various pathophysiological conditions.

scholarly journals Neurons and Glia in the Enteric Nervous System and Epithelial Barrier Function

Physiology ◽  
2018 ◽  
Vol 33 (4) ◽  
pp. 269-280 ◽  
Author(s):  
Nathalie Vergnolle ◽  
Carla Cirillo
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Barrier Function ◽  
Current Knowledge ◽  
The Body ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Epithelial Barrier Function ◽  
Exchange Surface

The intestinal epithelial barrier is the largest exchange surface between the body and the external environment. Its functions are regulated by luminal, and also internal, components including the enteric nervous system. This review summarizes current knowledge about the role of the digestive “neuronal-glial-epithelial unit” on epithelial barrier function.

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