ArticleJournal of Crohn's & colitis2021
Ileal Transcriptomic Analysis in Paediatric Crohn's Disease Reveals IL17- and NOD-signalling Expression Signatures in Treatment-naïve Patients and Identifies Epithelial Cells Driving Differentially Expressed Genes.
Article in Journal of Crohn's & colitis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Cytokine expression in subjects withFrontiers in cellular and infection microbiology · 2024Pooled it
- Disulfidptosis: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- TENTACLES: a consensus machine learning tool for robust biomarker discovery in heterogeneous data.BioData mining · 2026Article
- Identifying subtype-specific molecular pathways in Crohn's disease through RNA-seq and protein-protein interaction network analysis.Journal of translational autoimmunity · 2026Article
- Epigenetic biomarkers in inflammatory bowel diseases-computational challenges and opportunities.Journal of Crohn's & colitis · 2026Review
- Inflammation significantly alters mucosal transcriptomic signatures in pediatric inflammatory bowel disease.Crohn's & colitis 360 · 2026Article
- Novel Insights into the Pathogenesis of Inflammatory Bowel Diseases.Biomedicines · 2025Review
- Identification of Potential Functional Modules and Diagnostic Genes for Crohn's Disease Based on Weighted Gene Co-expression Network Analysis and LASSO Algorithm.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Multiomics Integration and Machine Learning Reveal Colony Stimulating Factor 3 Receptor as a Key Gene and Therapeutic Target in Crohn's Disease.Mediators of inflammation · 2025Article
- Dissecting the Mechanisms of Intestinal Immune Homeostasis by Analyzing T-Cell Immune Response in Crohn's Disease and Colorectal Cancer.Current gene therapy · 2024Article
- Hypomethylation and Overexpression of Th17-Associated Genes is a Hallmark of Intestinal CD4+ Lymphocytes in Crohn's Disease.Journal of Crohn's & colitis · 2023Article
- Supervised Machine Learning Classifies Inflammatory Bowel Disease Patients by Subtype Using Whole Exome Sequencing Data.Journal of Crohn's & colitis · 2023Article
- Recent developments in the assessment and management of inflammatory bowel disease in childhood: a narrative review.Translational pediatrics · 2023Review
- Integrated multiple microarray studies by robust rank aggregation to identify immune-associated biomarkers in Crohn's disease based on three machine learning methods.Scientific reports · 2023Article
- Distal Fecal Wash Host Transcriptomics Identifies Inflammation Throughout the Colon and Terminal Ileum.Cellular and molecular gastroenterology and hepatology · 2023Article
- Overexpression of Ubiquitin-Conjugating Enzyme E2C Is Associated with Worsened Prognosis in Prostate Cancer.International journal of molecular sciences · 2022Article
- Deleterious Genetic Variation Across the NOD Signaling Pathway Is Associated With Reduced NFKB Signaling Transcription and Upregulation of Alternative Inflammatory Transcripts in Pediatric Inflammatory Bowel Disease.Inflammatory bowel diseases · 2022Article
- Differential colitis susceptibility of Th1- and Th2-biased mice: A multi-omics approach.PloS one · 2022Article
- Identification and Validation of IFI44 as Key Biomarker in Lupus Nephritis.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsCrohn's disease [CD] arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD.
methodsWe employed contemporary targeted autoimmune RNA sequencing, in parallel to single-cell sequencing, to ileal tissue derived from paediatric CD and controls. Weighted gene co-expression network analysis [WGCNA] was performed and differentially expressed genes [DEGs] were determined. We integrated clinical data to determine co-expression modules associated with outcomes.
resultsIn all, 27 treatment-naive CD [TN-CD], 26 established CD patients and 17 controls were included. WGCNA revealed a 31-gene signature characterising TN-CD patients, but not established CD, nor controls. The CSF3R gene is a hub within this module and is key in neutrophil expansion and differentiation. Antimicrobial genes, including S100A12 and the calprotectin subunit S100A9, were significantly upregulated in TN CD compared with controls [p = 2.61 x 10-15 and p = 9.13 x 10-14, respectively] and established CD [both p = 0.0055]. Gene-enrichment analysis confirmed upregulation of the IL17-, NOD- and Oncostatin-M-signalling pathways in TN-CD patients, identified in both WGCNA and DEG analyses. An upregulated gene signature was enriched for transcripts promoting Th17-cell differentiation and correlated with prolonged time to relapse [correlation-coefficient-0.36, p = 0.07]. Single-cell sequencing of TN-CD patients identified specialised epithelial cells driving differential expression of S100A9. Cell groups, determined by single-cell gene expression, demonstrated enrichment of IL17-signalling in monocytes and epithelial cells.
conclusionsIleal tissue from treatment-naïve paediatric patients is significantly upregulated for genes driving IL17-, NOD- and Oncostatin-M-signalling. This signal is driven by a distinct subset of epithelial cells expressing antimicrobial gene transcripts.
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