1. Intercellular interaction between [FAP.sup.+] fibroblasts and [CD150.sup.+] inflammatory monocytes mediates fibrostenosis in Crohn's disease
- Author
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Ke, Bo-Jun, Abdurahiman, Saeed, Biscu, Francesca, Zanella, Gaia, Dragoni, Gabriele, Santhosh, Sneha, De Simone, Veronica, Zouzaf, Anissa, van Baarle, Lies, Stakenborg, Michelle, Bosakova, Veronika, Van Rymenant, Yenti, Verhulst, Emile, Verstockt, Sare, Klein, Elliott, Bislenghi, Gabriele, Wolthuis, Albert, Fric, Jan, Breynaert, Christine, D'Hoore, Andre, Van der Veken, Pieter, De Meester, Ingrid, Lovisa, Sara, Hawinkels, Lukas J.A.C., Verstockt, Bram, De Hertogh, Gert, Vermeire, Severine, and Matteoli, Gianluca
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Fibrosis -- Diagnosis -- Care and treatment ,Monocytes -- Health aspects ,Extracellular matrix -- Health aspects ,Transcription factors -- Health aspects ,Crohn's disease -- Diagnosis -- Care and treatment - Abstract
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., Introduction Crohn's disease (CD) is a chronic inflammatory condition affecting the gastrointestinal tract, characterized by transmural inflammation that often leads to complications such as strictures, fistulas, and abscesses. The disease [...]
- Published
- 2024
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