Whole-genome DNA methylation profiling of CD14+ monocytes reveals disease status and activity differences in Crohn’s disease patients
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001004221 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Crohn's disease (CD) is a multifactorial incurable chronic disorder. Current medical treatment seeks to induce and maintain a state of remission. During episodes of inflammation, monocytes infiltrate the inflamed mucosa whereupon they differentiate into macrophages with a pro-inflammatory phenotype. Here, we sought to characterize the circulating monocytes by profiling their DNA methylome and relate it to the level of CD activity. We gathered an all-female age-matched cohort of 16 CD patients and 7 non-CD volunteers. CD patients were further subdivided into 8 CD patients with active disease (CD-active) and 8 CD patients in remission (CD-remissive) as determined by the physician global assessment. We identified 15 and 12 differentially methylated genes (DMGs) when comparing CD with non-CD and CD-active with CD-remissive, respectively. Differential methylation was predominantly found in the promoter regions of inflammatory genes. Comparing our observations with gene expression data on classical (CD14++CD16-), non-classical (CD14+CD16++) and intermediate (CD14++CD16+) monocytes indicated that while 7 DMGs were differentially expressed across the 3 subsets, the remaining DMGs could not immediately be associated with differences in known populations. We conclude that CD activity is associated with differences in DNA methylation at the promoter region of inflammation-associated genes.
| S-EPMC7230341 | biostudies-literature
Project description:Whole-genome DNA methylation profiling of CD14+ monocytes obtained from CD-active, CD-remissive and non-CD individuals
| EGAD00010001846 | EGA
Project description:Background and Aims: Crohn’s disease [CD] and ulcerative colitis [UC] are distinct forms of inflammatory bowel disease. Heterogeneity of HLA-DR+SIRPα + mononuclear phagocytes [MNPs], including macrophages [MΦ], monocyte-derived [Mono] cells, and dendritic cells [DCs], was reported in gut tissue but not yet investigated in mesenteric lymph nodes [MLNs] of IBD patients. We here compared the phenotype, function, and molecular profile of HLA-DR+SIRPα+ MNPs in CD and UC MLNs. Methods: Cell distribution, morphology, immune function, and transcriptomic [bulk RNAseq] and high-dimensional protein expression profiles [CyTOF] of HLA-DR+SIRPα+ MNPs were examined in MLNs of UC [n = 14], CD [n = 35], and non-IBD [n = 12] patients. Results: Elevated frequencies of CD14+CD64+CD163+ [Mono/MΦ-like] MNPs displaying monocyte/ MΦ morphology and phagocytic function were a distinct feature of UC MLNs. In CD, the proportion of CD14-CD64-CD163- [DC-like] cells was augmented relative to Mono/MΦ-like cells; DC-like cells drove naïve T cell proliferation, Th1 polarisation, and Th17 TCM plasticity. Gene expression profile corroborated the nature of DC-like cells, best represented by BTLA, SERPINF, IGJ and, of Mono/MΦ- like cells, defined by CD163, MARCO, MAFB, CD300E, S100A9 expression. CyTOF analysis showed that CD123+ plasmacytoid cells predominated over conventional DCs in DC-like cells. Four CD163+ clusters were revealed in Mono/MΦ-like cells, two of which were enriched in MARCO-CD68dimHLA-DRdim monocyte-like cells and MARCOhiCD68hiHLA-DRhi Mɸ, whose proportion increased in UC relative to CD. Conclusions: Defining the landscape of MNPs in MLNs provided evidence for expansion of CD163+ Mono/MΦ-like cells in UC only, highlighting a distinction between UC and CD, and thus the potential contribution of monocyte-like cells in driving colitis.
2019-10-04 | GSE138364 | GEO
Project description:An untargeted liquid chromatography tandem mass spectrometry method was used to analyze the content of peptides with celiac disease (CD) active epitope in the five wheat species common wheat, spelt, durum wheat, emmer and einkorn. In total, 494 peptides with CD active epitope were identified. Relevant differences between the species concerning their CD immunoractive potential based on the distribution of CD-active epitopes and relative quantities of peptides with CD-active epitope were demonstrated.
2024-07-16 | PXD050917 | Pride
Project description:The expression of Triggering Receptor Expressed on Myeloid cells (TREM)-1 has been described as a predictive marker for anti-Tumor Necrosis Factor (TNF)-α monoclonal antibody (mAb) therapy responsiveness in patients with inflammatory bowel disease (IBD). Here we investigated expression of TREM-1 specifically in CD14+ monocytes in relation to anti-TNF response. The pretreatment TREM-1 expression levels of CD14+ monocytes of Crohn’s disease (CD) patients were predictive of outcome to anti-TNF mAb therapy, with low TREM-1 expression associated with response to anti-TNF. FACSorting of CD14+ monocytes with different TREM-1 levels showed that differentiation towards regulatory CD206+ M2 type macrophages by anti-TNF was suppressed in CD14+ monocytes with high TREM-1 expression. Activity of the Fcγ-Receptor and autophagy pathway, both necessary for M2 type differentiation and the response to anti-TNF, were decreased in CD14+ monocytes with high expression of TREM-1. We confirmed that the activity of the Fcγ-Receptor pathway was decreased in the CD patients that did not respond to anti-TNF therapy and that it was negatively correlated with TREM-1 expression levels in the CD patient cohort. In conclusion, our results indicate that TREM-1 expression levels in CD14+ monocytes associate with decreased autophagy and FcγR activity resulting in decreased differentiation to M2 type regulatory macrophages upon anti-TNF mAb treatment, which may explain anti-TNF non-response in IBD patients with high expression levels of TREM-1.
2021-04-07 | GSE165522 | GEO
Project description:Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal probes of 25 children and adolescents with active CD and 21 children without CD but with diverse intestinal afflictions as controls. We found that the transcriptomes of CD patients divide into three subgroups, a mixed group resembling part of control cases and a CD-low and CD-high groups referring to lower and higher levels of CD severity Despite generally increased inflammation, considerable variation in inflammation-level between subgroups was observed, which was further de-chiffred into immune cell types using immune cell de-convolution
2021-03-24 | GSE164883 | GEO
Project description:Background: Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to intestinal microbiota. To assess gut bacterial community, microRNA (miRNA), and short chain fatty acid (SCFA) signatures associated with the activity of Crohn’s disease (CD). Methods: DNA, miRNA, and metabolites were extracted from stool samples of 15 CD patients, eight with active disease and seven in remission, and nine healthy individuals. Microbial, miRNA and SCFA profiles were assessed using datasets from 16s rRNA sequencing, Nanostring miRNA and GC-MS targeted analysis, respectively. Results: Pairwise comparisons showed that 11 and 27 taxa differed between controls and CD patients with active and inactive disease, respectively. Seven taxa were common to both comparisons, whereas eight taxa differed in CD patients. α-Diversity was lower in both CD groups than in controls. The levels of 13 miRNAs differed (p-value <0.05; FC >1.5) in CD patients and controls. Comparisons of controls with CD patients having active and inactive disease identified 12 and seven significantly different miRNAs, respectively. Of six SCFAs, the levels of two differed significantly (p-value <0.05, FC >1.5) in CD patients and controls, and the levels of four differed in patients with active and inactive CD. PLS-DA revealed models with high discriminatory powers (AUC >0.9) for bacteria and miRNA. The levels of 14 miRNAs and 39 bacterial taxa correlated with the level of SCFAs. Conclusion: CD-related gut dysbiosis correlates significantly with miRNA and SCFA profiling, indicating complex relationships among all these factors in response to intestinal inflammation.
2020-08-10 | GSE144535 | GEO
Project description:We set out to detect a transcriptional signature in CD4 T cells of individuals at risk of progression to active tuberculosis. We indeed found such a signature which surprisingly could be tracked to a cell population expressing both T cell (CD3) and monocyte (CD14) markers. To identify the nature of the CD3+CD14+ population, we determined the transciptomic profile of single cells CD3-CD14+ Monocytes (n=21), CD3+D14- T cells (n=22), CD3+CD14+ cells in the Monocyte gate (Mgate) (n=22) and CD3+CD14+ cells in the lymphocyte gate (Lgate) (n=20) from one subject infected with latent tuberculosis by RNA sequencing. PCA on all genes showed that CD3+CD14+ cells represent an intermediate population between Monocytes and T cells, with CD3+CD14+ L gate cells closer to T cells compared to CD3+CD14+ Mgate cells.
2021-07-08 | GSE117435 | GEO
Project description:Biopsies from six individuals of each of the categories active CD (CDA), inactive CD (CD) and healthy controls (N) were analyzed for gene expression using microarray. The biopsies were obtained by ileo-colonoscopy and snap-frozen in nitrogen before RNA-isolation. A gastrointestinal pathologist classified the biopsies into normal, chronic active or chronic inactive inflammation based on Hematoxylin-Eosin stain of tissue sections from adjacent biopsies. Samples with discrepancy between endoscopic and histologic diagnoses were excluded from the final analysis, and uploaded with "NaN". The patients with chronic inactive inflammation all previously had verified CD of the terminal ileum. Patients coming to endoscopy for other reasons than IBD and with normal endoscopic and histological findings served as controls.
2019-05-01 | E-MTAB-6593 | biostudies-arrayexpress
Project description:Ulcerative colitis (UC) and Crohns disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies. To identify pathogenic processes underlying these disease subtypes, using single endoscopic pinch biopsies to estabolish 36 expression profiles, we elucidated gene expression patterns of active and inactive areas of UC and CD, and compared these to infectious colitis and healthy controls.To identify pathogenic processes underlying these disease subtypes, using single endoscopic pinch biopsies, we elucidated gene expression patterns of active and inactive areas of UC and CD, and compared these to infectious colitis and healthy controls. An unsupervised classification of a total of 36 samples yielded promising separation between IBD affected, unaffected, non-IBD colitis and normal controls, suggesting distinctive gene expression patterns for each sample type. The Significance Analysis of Microarays (SAM) software to select biologically significant changes in gene expression between groups. The criteria selected for SAM analysis are, a median false discovery rate (FDR) ? 0.00001%, fold change >2, and a Log2 mean expression index > 6.64.
2007-11-02 | E-GEOD-6731 | biostudies-arrayexpress