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Role of immune cells in intestinal fibrosis

Presented By
Dr B. Creyns, Catholic University Leuven, Leuven, Belgium
ECCO 2020

The relative contribution of innate and adaptive immune cells in the mucosa and deeper layers in fibrotic distal ileum of Crohn’s disease (CD) patients was assessed. The results show that inflammation in the deeper intestinal layers is different from the inflammatory signature seen in mucosal inflamed regions [1].

There is an urgent need for the identification of pathways and markers involved in fibrogenesis. As intestinal fibrosis mainly occurs in the deeper intestinal layers, immune cell characterisation of mucosal and deeper intestinal layers of the ileum was performed. The resected ileum of 17 CD and 6 colorectal cancer (CRC) patients undergoing right hemicolectomy were collected and divided in macroscopically inflamed and fibrotic tissue.

In 12 CD patients, an additional macroscopically inflamed region next to the fibrotic area was identified, with a lower fibrosis score than in the fibrotic area (4.0 vs 6.0; P=0.016). Both fibrotic and inflamed regions showed increased inflammation versus proximal unaffected CD and control (non-IBD) ileum (4.0 and 4.5 vs 1.0 and 0.0; P<0.001 for all). In the inflamed ileum, no differences in immune populations were observed between mucosa and deeper layers. In contrast, CD19-positive B cells were specifically enriched in fibrotic ileum versus proximal CD mucosa (32.2% vs 20.4% of CD45-positive cells; P=0.008). In the deeper layers of fibrostenotic CD ileum, alternative innate immune cells, such as mature CD11c-postive dendritic cells (P=0.042) and CD206-positive macrophages (P<0.001), were enriched compared to the mucosa overlying the fibrotic tissue. The authors concluded that, as these cells are specifically expanded in the deeper intestinal layers, this finding may lead to identifying targets for new anti-fibrotic therapies.

    1. Creyns B, et al. ECCO-IBD 2020, DOP83.

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