| Citace |
KE, Bo-Jun, Saeed ABDURAHIMAN, Francesca BISCU, Gaia ZANELLA,
Gabriele DRAGONI, Sneha SANTHOSH, De Simone VERONICA, Anissa
ZOUZAF, van Baarle LIES, Michelle STAKENBORG, Veronika
BOSÁKOVÁ, Van Rymenant YENTL, Emile VERHULST, Sare VERSTOCKT,
Elliott KLEIN, Gabriele BISLENGHI, Albert WOLTHUIS, Jan FRIČ,
Christine BREYNAERT, Andre D'HOORE, van der Veken PIETER, De
Meester INGRID, Sara LOVISA, Lukas J A C HAWINKELS, Bram
VERSTOCKT, De Hertogh GERT, Severine VERMEIRE a Gianluca
MATTEOLI. Intercellular interaction between FAP+ fibroblasts
and CD150+inflammatory monocytes mediates fibrostenosis in
Crohn's disease. Journal of Clinical Investigation. Ann Arbor:
AMER SOC CLINICAL INVESTIGATION INC, 2024, roč. 134, č. 16, s.
1-19. ISSN 0021-9738. Dostupné z:
https://dx.doi.org/10.1172/JCI173835. |
| Popis |
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.
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