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.

P459 Expression of SerpinE1, a potential new disease activity marker, reflects therapeutic response in Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S453-S453
Author(s):  
B Jójrt ◽  
T Molnár ◽  
V Szabó ◽  
Á Varga ◽  
T Resál ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Healthy Subjects ◽  
Expression Patterns ◽  
Invasive Disease ◽  
Gene Expressions ◽  
Inflammatory Bowel ◽  
Active Disease ◽  
Control Samples

Abstract Background Inflammatory Bowel Disease (IBD) occurs as a consequence of abnormal immune response generating unbalance between pro- and anti-inflammatory signalling. Analysis of cytokine profiles in view of different cytokine targeting or immunosuppressive therapy may open up new therapeutic targets and may reveal biological profiles that distinguish responders from non-responders before initiating therapy. The aim of present study was to determine cytokine profile of IBD patients and identify cytokines with predictive potential. Methods IBD patients with clinically active disease were enrolled in study. Blood and biopsy samples were obtained from 22 IBD patients and 5 healthy controls. Biopsies were taken from inflamed and non-inflamed part of colon of IBD patients. Total protein and mRNA were isolated from biopsy samples. Cytokine Array was used to analyse cytokine expression patterns. Serum and mucosal SerpinE1 levels were measured by ELISA and qRT-PCR. Results In samples from IBD patients, remarkable discrimination between inflamed, or non-inflamed areas was observed, whereas no pro-inflammatory cytokines were detected in control samples. SerpinE1 was presented in every inflamed biopsy samples, which was analyzed in more details. Mucosal expression of SerpinE1 differed significantly in healthy subjects compared to IBD patients with active disease (0 vs 24.06 pg/mg, p=0.02). After therapy induction a remarkable decrease was observed in the mucosal SerpinE1 concentration in responders (45.5 vs 9.7 pg/mg, p=0.02) versus non-responders (45 vs 61.2 pg/mg, p=0.3). Moreover, mean value of mucosal SerpinE1 did not differ significantly in healthy subjects compared to responders (5.7 vs. 0 pg/mg, p=0.12). In non-responders the fold changes of SerpinE1 gene expressions were significantly (p=0.001) higher than in responders. Lowest expression of SerpinE1 gene was measured in control samples, whereas the highest in untreated, inflamed biopsy samples. Serum and mucosal SerpinE1 concentrations were significantly higher in patients with active disease compared to inactive (tissue: 5 vs 47.4 pg/mg, p=0.00003; serum: 22.4 vs 25.94 mg/ml, p=0.022). Correlation analysis revealed that serum SerpinE1 correlates with disease activity (p<0,01, cut-off value: 22 mg/ml, sensitivity=80%, specificity=60%, accuracy=74%), whereas no correlation was observed between the mucosal SerpineE1 concentration and the disease activity (p>0.1, sensitivity=72%, specificity=77.8%, accuracy=73.5%). Conclusion These results suggest that serum and mucosal SeprinE1 expression reflects endoscopic activity of IBD. Correlation of SerpinE1expression between the blood and the bowel mucosa would open up new possibilities in non-invasive disease monitoring of IBD.

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 Evaluation of anti-TNF therapeutic response in patients with inflammatory bowel disease: Current and novel biomarkers

EBioMedicine ◽  
2021 ◽  
Vol 66 ◽  
pp. 103329
Author(s):  
Guanglin Cui ◽  
Qingbo Fan ◽  
Zhenfeng Li ◽  
Rasmus Goll ◽  
Jon Florholmen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Response ◽  
Novel Biomarkers ◽  
Inflammatory Bowel

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.

scholarly journals Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease

2008 ◽  
Vol 105 (46) ◽  
pp. 17931-17936 ◽  
Author(s):  
Danyvid Olivares-Villagómez ◽  
Yanice V. Mendez-Fernandez ◽  
Vrajesh V. Parekh ◽  
Saif Lalani ◽  
Tiffaney L. Vincent ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Genetic Model ◽  
Critical Role ◽  
Intraepithelial Lymphocytes ◽  
Lymphocyte Function ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8αα homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.

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