作者
B J Ke,Saeed Abdurahiman,Francesca Biscu,Gabriele Dragoni,Sneha Santhosh,Veronica De Simone,Anissa Zouzaf,Lies van Baarle,Michelle Stakenborg,Veronika Bosáková,Yentl Van Rymenant,Emile Verhulst,Sare Verstockt,Gabriele Bislenghi,Albert Wolthuis,Jan Frič,Christine Breynaert,André D’Hoore,Pieter Van der Veken,Ingrid De Meester,Bram Verstockt,Gert De Hertogh,Séverine Vermeire,Gianluca Matteoli
摘要
SUMMARY Crohn’s disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibro-stenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate complex intercellular interactions leading to fibro-stenosis in CD, we analysed the transcriptome of cells isolated from the transmural ileum of CD patients, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from non-CD patients. Our computational analysis revealed that pro-fibrotic signals from a subset of monocyte-derived cells expressing CD150 induce 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) production. Therapeutic inhibition of TWIST1 inhibits fibroblast activation, reducing ECM production and deposition. These findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibro-stenosis in CD.