scholarly journals Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease

2020 ◽  
Vol 14 (7) ◽  
pp. 995-1009 ◽  
Author(s):  
M C Barnhoorn ◽  
S K Hakuno ◽  
R S Bruckner ◽  
G Rogler ◽  
L J A C Hawinkels ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stromal Cells ◽  
Bowel Disease ◽  
Immune Cell ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Clinical Settings ◽  
Intestinal Epithelial ◽  
Stromal Compartment ◽  
Inflammatory Bowel

Abstract Up till now, research on inflammatory bowel disease [IBD] has mainly been focused on the immune cells present in the gastrointestinal tract. However, recent insights indicate that stromal cells also play an important and significant role in IBD pathogenesis. Stromal cells in the intestines regulate both intestinal epithelial and immune cell homeostasis. Different subsets of stromal cells have been found to play a role in other inflammatory diseases [e.g. rheumatoid arthritis], and these various stromal subsets now appear to carry out also specific functions in the inflamed gut in IBD. Novel potential therapies for IBD utilize, as well as target, these pathogenic stromal cells. Injection of mesenchymal stromal cells [MSCs] into fistula tracts of Crohn’s disease patients is already approved and used in clinical settings. In this review we discuss the current knowledge of the role of stromal cells in IBD pathogenesis. We further outline recent attempts to modify the stromal compartment in IBD with agents that target or replace the pathogenic stroma.

scholarly journals The Possible Role of the Novel Cytokines IL-35 and IL-37 in Inflammatory Bowel Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yanmei Li ◽  
Yanan Wang ◽  
Ying Liu ◽  
Yatian Wang ◽  
Xiuli Zuo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Healthy Subjects ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Intestinal Epithelial ◽  
Gene Expressions ◽  
Expression Studies ◽  
Novel Biomarkers ◽  
Inflammatory Bowel

Interleukin- (IL-) 35 and IL-37 are newly discovered immune-suppressing cytokines. They have been described in inflammatory diseases such as collagen-induced arthritis and asthma. However, their expressions in inflammatory bowel disease (IBD) patients have not been yet explored. Our aim was to evaluate serum and inflamed mucosal levels in IBD patients. In 20 ulcerative colitis (UC) patients, 7 Crohn’s disease (CD) patients, and 15 healthy subjects, cytokine levels in serum were determined using ELISA and mucosal expression studies were performed by immunohistochemistry, quantitative real-time PCR, and Western blot. The results showed that serums IL-35 and IL-37 levels were significantly decreased in UC and CD patients compared with healthy subjects. The cytokines levels correlated inversely with UC activity. IL-35 was expressed in infiltrating immune cells while IL-37 in intestinal epithelial cells as well as inflammatory cells. IBD patients had significantly higherEbi3,p35(two subunits of IL-35), andIL-37bgene expressions; IL-35 and IL-37 protein expressions were higher in IBD patients compared with controls. The study showed that serums IL-35 and IL-37 might be potentially novel biomarkers for IBD. Intestinal IL-35 and IL-37 proteins are upregulated, suggesting that regulating the expression of the two cytokines may provide a new possible target for the treatment of IBD.

scholarly journals P059 Cytokine responsive transcriptional networks in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S164-S164
Author(s):  
A Treveil ◽  
P Pavlidis ◽  
A Tsakmaki ◽  
G Bewick ◽  
T Korcsmaros ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Mucosal Healing ◽  
Mucosal Barrier ◽  
Transcriptional Networks ◽  
Intestinal Epithelial ◽  
Transcriptomics Data ◽  
Inflammatory Bowel ◽  
Regulatory Effects

Abstract Background Interactions between the immune system and the intestinal epithelium play an important role in the pathogenesis of chronic immune mediated inflammatory diseases, including inflammatory bowel disease (IBD). In IBD, debilitating symptoms and complications including abscesses and cancer are associated with aberrant cytokine production and resulting intestinal epithelial damage. Despite the advent of biological therapies targeting key pathogenic cytokines, like tumour necrosis α (TNF), only 18% of IBD patients will achieve complete disease control and mucosal healing. Here, we provide new insights into the epithelial response to cytokines using network analysis of transcriptomics data from colonic organoids (colonoids). Methods We generated an atlas of the transcriptomic effects of cytokines by treating human-derived colonoids with IFNg, IL13, IL9, IL17A and TNF (independently). By integrating the observed transcriptional changes with previously published signalling and regulatory interactions, we generated causal networks to elucidate the effect of cytokine cues on epithelial cells. These networks comprised experimentally verified protein–protein and transcription factor (TF)–target gene interactions, forming signalling pathways linking cytokines to TFs and from TFs to differentially expressed genes. Results With this analysis, we identified previously unrecognised levels of shared and distinct transcriptional regulation of colonic epithelial function by different cytokines. While IL9 had a negligible impact on the transcriptome, the transcripts with differential expression induced by IFNg, IL13, IL17A or TNF were consistent with their recognised function in other tissues. IFNg and TNF exhibited similar magnitude and directional effects on key immune pathways while IL13 had the opposite effect. Using a network approach, we found that regulatory effects of cytokines are primarily transduced through unique signalling routes, some of which converge on the same key transcription factors; CEBPA, E2F1, E2F2, ETS1, FOS, IRF1 and MAZ. We observed independent regulatory mechanisms of the different cytokines as well as complementarity in the epithelial responses regulated by different canonical cytokines. Conclusion The generated cytokine transcriptional atlas provides a unique insight into the immune-epithelial interactome by allowing the identification of shared and distinct transcriptional pathways across different types of immunity at the mucosal barrier. In addition, it provides the unique opportunity to study cytokine responses in the context of human disease and generate novel hypotheses.

Slc26a3 (DRA) in the Gut: Expression, Function, Regulation, Role in Infectious Diarrhea and Inflammatory Bowel Disease

2020 ◽  
Author(s):  
Qin Yu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Current Knowledge ◽  
Cloning And Expression ◽  
Intestinal Epithelial ◽  
Infectious Diarrhea ◽  
Luminal Membrane ◽  
Inflammatory Bowel ◽  
Future Therapy

Abstract Background The transport of transepithelial Cl- and HCO3- is crucial for the function of the intestinal epithelium and maintains the acid-based homeostasis. Slc26a3 (DRA), as a key chloride-bicarbonate exchanger protein in the intestinal epithelial luminal membrane, participates in the electroneutral NaCl absorption of intestine, together with Na+/H+ exchangers. Increasing recent evidence supports the essential role of decreased DRA function or expression in infectious diarrhea and inflammatory bowel disease (IBD). Method In this review, we give an overview of the current knowledge of Slc26a3, including its cloning and expression, function, roles in infectious diarrhea and IBD, and mechanisms of actions. A better understanding of the physiological and pathophysiological relevance of Slc26a3 in infectious diarrhea and IBD may reveal novel targets for future therapy. Conclusion Understanding the physiological function, regulatory interactions, and the potential mechanisms of Slc26a3 in the pathophysiology of infectious diarrhea and IBD will define novel therapeutic approaches in future.

scholarly journals Lactobacillus Reuteri DSM 17938 (Limosilactobacillus reuteri) in Diarrhea and Constipation: Two Sides of the Same Coin?

Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 643
Author(s):  
Angela Saviano ◽  
Mattia Brigida ◽  
Alessio Migneco ◽  
Gayani Gunawardena ◽  
Christian Zanza ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Emergency Department ◽  
Abdominal Pain ◽  
Human Health ◽  
Bowel Disease ◽  
Chronic Constipation ◽  
Lactobacillus Reuteri ◽  
Current Knowledge ◽  
Gastrointestinal Symptoms ◽  
Inflammatory Bowel

Background and Objectives: Lactobacillus reuteri DSM 17938 (L. reuteri) is a probiotic that can colonize different human body sites, including primarily the gastrointestinal tract, but also the urinary tract, the skin, and breast milk. Literature data showed that the administration of L. reuteri can be beneficial to human health. The aim of this review was to summarize current knowledge on the role of L. reuteri in the management of gastrointestinal symptoms, abdominal pain, diarrhea and constipation, both in adults and children, which are frequent reasons for admission to the emergency department (ED), in order to promote the best selection of probiotic type in the treatment of these uncomfortable and common symptoms. Materials and Methods: We searched articles on PubMed® from January 2011 to January 2021. Results: Numerous clinical studies suggested that L. reuteri may be helpful in modulating gut microbiota, eliminating infections, and attenuating the gastrointestinal symptoms of enteric colitis, antibiotic-associated diarrhea (also related to the treatment of Helicobacter pylori (HP) infection), irritable bowel syndrome, inflammatory bowel disease, and chronic constipation. In both children and in adults, L. reuteri shortens the duration of acute infectious diarrhea and improves abdominal pain in patients with colitis or inflammatory bowel disease. It can ameliorate dyspepsia and symptoms of gastritis in patients with HP infection. Moreover, it improves gut motility and chronic constipation. Conclusion: Currently, probiotics are widely used to prevent and treat numerous gastrointestinal disorders. In our opinion, L. reuteri meets all the requirements to be considered a safe, well-tolerated, and efficacious probiotic that is able to contribute to the beneficial effects on gut-human health, preventing and treating many gastrointestinal symptoms, and speeding up the recovery and discharge of patients accessing the emergency department.

scholarly journals Hyperactive chemotaxis contributes to anti-TNFα treatment resistance in inflammatory bowel disease

2021 ◽  
Author(s):  
Tung On Yau ◽  
Jayakumar Vadakekolathu ◽  
Gemma Ann Foulds ◽  
Guodong Du ◽  
Christos Polytarchou ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Immune Cell ◽  
Treatment Resistance ◽  
Enrichment Analysis ◽  
Cell Populations ◽  
Treated Animal ◽  
Necrosis Factor Alpha ◽  
Potential Biomarker ◽  
Inflammatory Bowel

Background & Aims Anti-tumour necrosis factor-alpha (anti-TNFα) agents have been used for inflammatory bowel disease (IBD), however, it has up to 30% non-response rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNFα treatment are clearly needed. Methods Publicly available transcriptomic data from IBD patients receiving anti-TNFα therapy was systemically collected and integrated. In silico flow cytometry approaches and MetaScape were applied to evaluate immune cell populations and to perform gene enrichment analysis, respectively. Genes identified within enrichment pathways validated in neutrophils were tracked in an anti TNFα-treated animal model (with lipopolysaccharide (LPS)-induced inflammation). The receiver operating characteristic (ROC) curve was applied to all genes to identify the best prediction biomarkers. Results A total of 449 samples were retrieved from control, baseline and after primary anti-TNFα therapy or placebo. No statistically significant differences were observed between anti-TNFα treatment responders and non-responders at baseline in immune microenvironment scores. Neutrophils, endothelial and B cell populations were higher in baseline non-responders and chemotaxis pathways may contribute to the treatment resistance. Genes related to chemotaxis pathways were significantly up-regulated in LPS-induced neutrophils but no statistically significant changes were observed in neutrophils treated with anti-TNFα. Interleukin 13 receptor subunit alpha 2 (IL13RA2) is the best predictor (ROC: 80.7%, 95% CI: 73.8% - 87.5%) with a sensitivity of 68.13% and specificity of 84.93%, and significantly higher in non-responders compared to responders (p < 0.0001). Conclusions Hyperactive chemotaxis influences responses to anti TNFα treatment and IL13RA2 is a potential biomarker to predict anti-TNFα treatment response.

scholarly journals Cardiovascular risks in patients with inflammatory bowel disease: what should be taken into account?

2021 ◽  
Vol 1 (6) ◽  
pp. 112-120
Author(s):  
G. B. Bikbavova ◽  
M. A. Livzan
Keyword(s):  
Cardiovascular Disease ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Treat To Target ◽  
Steady Increase ◽  
Cardiovascular Risks ◽  
Specialized Care ◽  
Pathogenetic Therapy ◽  
Inflammatory Bowel

In recent years, there has been a steady increase in the incidence of inflammatory bowel disease (IBD) worldwide. Treatment of ulcerative colitis and Crohn’s disease has become more effective thanks to the emergence of biological therapies, increased access to specialized care and a “treat to target” approach. However, with an increase in the life expectancy of patients with IBD, there is an increase in the number of persons with comorbidity, primarily with a combination of IBD with cardiovascular pathology. Environmental factors lead to a change in the diversity and density of colonization of the intestinal microbiota, a violation of its barrier function, immune dysregulation, which in turn leads to the development of chronic inflammatory diseases and atherosclerosis. Levels of proinflammatory cytokines, C-reactive protein, and homocysteine increase in IBD, leading to endothelial dysfunction and atherosclerosis. In addition, inflammatory processes in IBD promote hypercoagulation, which occurs both in the thromboembolic complications and in the pathogenesis of the disease itself. It has been suggested that medical pathogenetic therapy for IBD is also associated with the risk of cardiovascular disease. In this review, we systematize the available data on the risks of cardiovascular diseases in patients with IBD. A literature search containing information on relevant studies was carried out in PubMed and Google Scholar systems with the keywords: inflammatory bowel disease, cardiovascular disease, inflammation, atherosclerosis.

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