Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.
- MeSH
- Crohnova nemoc * metabolismus patologie imunologie MeSH
- dospělí MeSH
- endopeptidasy metabolismus genetika MeSH
- extracelulární matrix metabolismus patologie MeSH
- fibroblasty * metabolismus patologie MeSH
- fibróza * MeSH
- ileum patologie metabolismus imunologie MeSH
- jaderné proteiny metabolismus genetika MeSH
- lidé MeSH
- mezibuněčná komunikace MeSH
- monocyty * metabolismus patologie imunologie MeSH
- myši MeSH
- receptory buněčného povrchu metabolismus genetika MeSH
- transkripční faktor Twist * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
