Intestinal epithelial expression of human TNF is sufficient to induce small bowel inflammation and sacroiliitis mimicking human Spondyloarthritis.

Autor:	Debusschere K; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Souza D; Department of Immunology and Respiratory Diseases Research, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA., Nabozny GH; Department of Immunology and Respiratory Diseases Research, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA., Dumas E; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Verheugen E; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Coudenys J; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Manuello T; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Stappers F; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Decruy T; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Maelegheer M; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Schryvers N; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Gilis E; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium., Elewaut D; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; VIB-UGent Center for Inflammation Research, Unit for Molecular Immunology and Inflammation, Ghent, Belgium.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Sep 18. Date of Electronic Publication: 2024 Sep 18.
DOI:	10.1093/rheumatology/keae507
Abstrakt:	Objectives: Gut and joint disease commonly co-occur in spondyloarthritis (SpA). Up to 50% of SpA-patients show signs of subclinical gut inflammation and 10% evolves into inflammatory bowel disease (IBD). However, the mechanisms underlying this gut-joint axis are still unclear. Here we tested the hypothesis whether restricted expression of a pro-inflammatory cytokine in the intestine may trigger onset of combined gut and joint inflammation. Methods: Intestinal expression of human TNF (hTNF) was achieved by driving hTNF gene expression under control of the rat FAPB2 promoter, creating a new animal model, the TNFgut mice, which 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, qPCR 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 T helper 17 and regulatory T cells, 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 nor 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 spondyloarthritis. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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