Fibrostricturing Crohn's disease is marked by an increase in active eosinophils in the deeper layers

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

doi:10.14309/ctg.0000000000000706

Fibrostricturing Crohn's disease is marked by an increase in active eosinophils in the deeper layers

Clin Transl Gastroenterol. 2024 May 1. doi: 10.14309/ctg.0000000000000706. Online ahead of print.

Authors

Inge Jacobs^{1

2}, Bo-Jun Ke², Matthias Ceulemans², Jonathan Cremer¹, André D'Hoore³, Gabriele Bislenghi³, Gianluca Matteoli², Gert De Hertogh⁴, João Sabino^{2

3}, Marc Ferrante^{2

3}, Séverine Vermeire^{2

3}, Christine Breynaert^{1

5}, Tim Vanuytsel^{2

3}, Bram Verstockt^{2

3}

Affiliations

¹ KU Leuven, Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, Leuven, Belgium.
² KU Leuven, Department of Chronic Diseases and Metabolism (ChroMetA), Translational Research Centre for Gastrointestinal Disorders (TARGID), Leuven, Belgium.
³ University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.
⁴ KU Leuven, Department of Imaging and Pathology, Translational Cell & Tissue Research, Leuven, Belgium.
⁵ University Hospitals Leuven, Department of General Internal Medicine, Leuven, Belgium.

PMID: 38690831
DOI: 10.14309/ctg.0000000000000706

Abstract

Introduction: Approximately 50% of Crohn's disease (CD) patients 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 CD patients.

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

Results: The Masson's Trichrome staining confirmed augmented collagen deposition in both the fibrotic as the inflamed region, though with a significant increased collagen deposition in fibrotic compared to inflamed tissue. Distinct Th1, Th2, regulatory T cells, dendritic cells and monocytes were identified in fibrotic and inflamed CD ileum compared to unaffected ileum of CD patients as non-IBD controls. Only minor differences were observed between fibrotic and inflamed tissue, with more active eosinophils in fibrotic deeper layers and increased Eosinophil Cationic Protein (ECP) protein expression in inflamed deeper layers. Lastly, no differences in eosinophil and fibroblast co-localization was observed between the different regions.

Conclusion: This study characterized immune cell distribution and protein expression in fibrotic and inflamed ileal tissue of CD patients. Immunologic, proteomic and histological data suggest inflammation and fibrosis are intertwined, with 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.