Crohn’s disease is a long-term disease that affects around 1 in every 650 people, in which parts of the gut become swollen, inflamed, and ulcerated. When ulcers or inflammation in the intestinal wall fail to heal properly, Crohn’s fistulas can form, burrowing into surrounding tissue and sometimes connecting to other organs or the skin. Precisely how these form, grow and persist has remained unclear, and they are very challenging to treat.
In this study, published in Nature, researchers analysed thousands of individual cells from Crohn’s fistulas, comparing them with healthy gut tissue. Using advanced single-cell and spatial analysis techniques, the team, led by the Simmons and Antanaviciute Groups, mapped the precise composition and behaviour of cells within the fistula tracts.
They discovered that fistulas are lined by concentric rings of “rogue” fibroblasts – cells that normally maintain tissue structure – that have become reprogrammed to act like cells involved in early fetal gut development. This out-of-context activity caused fibroblasts near the tract surface to destroy the surrounding tissue, promoting tunnelling, while deeper fibroblasts produced stiff, fibrotic material that stabilised and maintained the tunnels.
Read the full story on the MRC Weatherall Institute of Molecular Medicine (MRC WIMM) website.