Clin Transl Gastroenterol. 2024 Jul 12. doi: 10.14309/ctg.0000000000000706.Online ahead of print.

Inge Jacobs ^1 2, Bo-Jun Ke ², Matthias Ceulemans ², Jonathan Cremer ¹, André D'Hoore ³, Gabriele Bislenghi ³, Gianluca Matteoli ², Gert De Hertogh ⁴, João Sabino ^2 3, Marc Ferrante ^2 3, Séverine Vermeire ^2 3, Christine Breynaert ^1 5, Tim Vanuytsel ^2 3, Bram Verstockt ^2 3

Author information

¹Katholieke Universiteit Leuven, Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, Leuven, Belgium.

²Katholieke Universiteit Leuven, Department of Chronic Diseases and Metabolism (ChroMetA), Translational Research Centre for Gastrointestinal Disorders (TARGID), Leuven, Belgium.

³University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.

⁴Katholieke Universiteit Leuven, Department of Imaging and Pathology, Translational Cell & Tissue Research, Leuven, Belgium.

⁵University Hospitals Leuven, Department of General Internal Medicine, Leuven, Belgium .

Abstract

Introduction: Approximately 50% of patients with Crohn's disease (CD) develop intestinal strictures necessitating surgery. The immune cell distribution in these strictures remains uncharacterized. We aimed to identify the immune cells in intestinal strictures of patients with CD.

Methods: During ileocolonic resections, transmural sections of terminal ileum were sampled from 25 patients with CD and 10 non-inflammatory bowel disease controls. Macroscopically unaffected, fibrostenotic, and inflamed ileum was collected and analyzed for immune cell distribution (flow cytometry) and protein expression. Collagen deposition was assessed through a Masson Trichrome staining. Eosinophil and fibroblast colocalization was assessed through immunohistochemistry.

Results: The Masson Trichrome staining confirmed augmented collagen deposition in both the fibrotic and the inflamed regions, though with a significant increased collagen deposition in the fibrotic compared with inflamed tissue. Distinct Th1, Th2, regulatory T cells, dendritic cells, and monocytes were identified in fibrotic and inflamed CD ileum compared with unaffected ileum of patients with CD as non-inflammatory bowel disease controls. Only minor differences were observed between fibrotic and inflamed tissue, with more active eosinophils in fibrotic deeper layers and increased eosinophil cationic protein expression in inflamed deeper layers. Last, no differences in eosinophil and fibroblast colocalization were observed between the different regions.

Discussion: This study characterized immune cell distribution and protein expression in fibrotic and inflamed ileal tissue of patients with CD. Immunologic, proteomic, and histological data suggest inflammation and fibrosis are intertwined, with a large overlap between both tissue types. However strikingly, we did identify an increased presence of active eosinophils only in the fibrotic deeper layers, suggesting their potential role in fibrosis development.