MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model

Mamie, Céline; Bruckner, Ramona S; Lang, Silvia; Shpigel, Nahum Y.; Turina, Matthias; Rickenbacher, Andreas; Cabalzar-Wondberg, Daniela; Chvatchko, Yolanda; Rogler, Gerhard; Scharl, Michael

doi:10.1080/21688370.2021.1994350

Cited by 2 publications

(1 citation statement)

References 30 publications

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“…Histopathological findings showed remarkable similarities with CD-associated fistulae, including evidence for EMT immunohistochemically. 78 Although promising, this model requires further validation and replication. Several mouse models of non-intestinal fistula exist including trachea-esophageal 79 and vascular fistulae, 80 which may also serve to inform development of future CD models.…”

Section: Cytokine Profilementioning

confidence: 99%

Pathogenesis of Fistulating Crohn’s Disease: A Review

McGregor

Tandon

Simmons

2023

Cellular and Molecular Gastroenterology and Hepatology

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Section: Cytokine Profilementioning

confidence: 99%

Pathogenesis of Fistulating Crohn’s Disease: A Review

McGregor

Tandon

Simmons

2023

Cellular and Molecular Gastroenterology and Hepatology

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Spatial Single Cell Profiling Using Imaging Mass Cytometry: Inflammatory Versus Penetrating Crohn’s Disease

Lehmann,

Weixler,

Elezkurtaj

et al. 2024

Journal of Crohn's and Colitis

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Background and aims Fistula formation is a major complication in Crohn’s disease (CD) and the role of the immune cell compartment remains to be elucidated. Thus, we compared the immune-cell compartment of CD fistula to inflammatory CD colitis using imaging mass cytometry and immunofluorescence. Methods A 36-marker panel including structural, functional and lineage markers for use in imaging mass cytometry (IMC) was established. This panel was applied to analyze paraffin-embedded CD fistula tract (n=11), CD colitis (n=10), and colon samples from non-inflamed controls (n=12). Computational methods for cell segmentation, dimensionality reduction and cell type clustering were used to define cell populations for cell frequency, marker distribution and spatial neighborhood analysis. Multiplex immunofluorescence was used for higher resolution spatial analysis. Results Analysis of cell frequencies in CD fistulas compared to CD colitis and control colonic samples revealed a significant increase in neutrophils, effector cytotoxic T cells and inflammatory macrophages in CD fistula samples, whereas regulatory T cells were decreased. Neutrophils in CD fistula expressed significantly more matrix metalloproteinase 9 (MMP9), correlating to extracellular matrix remodeling. Neighborhood analysis revealed a strong association between MMP9+ neutrophils and effector cytotoxic T cells in both CD fistulas and colitis. Conclusions This study presents the first highly multiplexed single cell analysis of the immune-cell compartment of CD fistulas and their spatial context. It links immune cell dynamics, particularly MMP9+ neutrophils, to extracellular matrix remodeling in CD fistulas, offering insights into the complex network of cellular interactions and potential therapeutic targets for CD complications.

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MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model

Cited by 2 publications

References 30 publications

Pathogenesis of Fistulating Crohn’s Disease: A Review

Pathogenesis of Fistulating Crohn’s Disease: A Review

Spatial Single Cell Profiling Using Imaging Mass Cytometry: Inflammatory Versus Penetrating Crohn’s Disease

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