Intercellular interaction between FAP+ fibroblasts and CD150+ inflammatory monocytes mediates fibrostenosis in Crohn's disease.
J Clin Invest
; 134(16)2024 Jul 23.
Article
in En
| MEDLINE
| ID: mdl-39042469
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fibrosis
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Monocytes
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Crohn Disease
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Twist-Related Protein 1
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Fibroblasts
Limits:
Adult
/
Animals
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Female
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Humans
/
Male
Language:
En
Journal:
J Clin Invest
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: