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Updated: Jun 12, 2025
A TNBS-Induced Rodent Model to Study the Pathogenic Role of Mechanical Stress in Crohn's Disease
Published on: March 1, 2022
Intestinal epithelial expression of human TNF is sufficient to induce small bowel inflammation and sacroiliitis,
Karlijn Debusschere1,2, Donald Souza3, Gerald H Nabozny3
1Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Objectives:
Gut and joint disease commonly co-occur in SpA. Up to 50% of patients with SpA show signs of subclinical gut inflammation, of which 10% develops IBD. However, the mechanisms underlying this gut-joint axis are still unclear. Here we investigated the hypothesis that restricted expression of a pro-inflammatory cytokine in the intestine may trigger the onset of combined gut and joint inflammation.
Methods:
Intestinal expression of human TNF (hTNF) was achieved by driving hTNF gene expression using the rat FAPB2 promoter, creating a new animal model, TNFgut mice, that expresses hTNF in the proximal intestinal tract. Intestinal-specific TNFgut mice were examined for pathological changes in the intestine and extra-intestinal tissues by means of histology, reverse transcription PCR (RT-PCR) and flow cytometry, along with 16S sequencing on stools.
Results:
Local expression of hTNF in the epithelium of the small intestine induces a pro-inflammatory state of the proximal intestinal tract, with epithelial alterations and induction of members of the S100 family, as well as local upregulation of Th17 and Treg, but no obvious signs of dysbiosis. Curiously, TNFgut mice develop sacroiliitis (P <0.05) in addition to small bowel inflammation (P <0.05). However, no signs of peripheral arthritis or enthesitis could be documented.
Conclusion:
Intestinal expression of hTNF is sufficient to initiate a pro-inflammatory cascade culminating in small bowel inflammation and sacroiliitis. Thus, gut-derived cytokines are sufficient to induce SpA.
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