TWISTed fibroblasts: New drivers of intestinal fibrosis in Crohn's disease

Abstract

Fibrosis is the pathological consequence of chronic inflammation. In Crohn's disease (CD), fibrostenotic complications occur with 50–70 % frequency as a failure to properly repair the tissue damage. Intestinal stenosis requires surgical intervention and relapses in most patients. Mesenchymal cells encompassed of heterogeneous cell subsets orchestrate this complex process. The lack of a full characterization of the stromal diversity and function in CD has consequently slowed the development of anti-fibrotic targets. Two recent studies align together demonstrating FAP+TWIST1+ fibroblasts as the primary mesenchymal population driving intestinal fibrosis in CD. Genetic and pharmacological targeting of Twist1 in mouse models proved the functional role of Fap+Twist1+ fibroblasts and indicate the use of the Twist1 inhibitor harmine as a potential therapeutic strategy to revert fibrosis.

Keywords

• Fibroblasts
• Twist
• Intestinal fibrosis
• Crohn's disease