The following is a summary of “Spatial single cell profiling using imaging mass cytometry – inflammatory versus penetrating Crohn’s disease,” published in the March 2024 issue of Gastroenterology by Lehmann et al.
Crohn’s disease (CD) patients frequently develop fistulas, and the involvement of immune cells is not yet fully understood.
Researchers started a retrospective study to compare the immune cell makeup of CD fistulas with inflammatory CD colitis using advanced imaging mass cytometry (IMC).
They established a 36-marker panel encompassing structural, functional, and lineage markers for application in IMC. Panel underwent analysis on paraffin-embedded CD fistula tract (n=11), CD colitis (n=10), and colon samples from non-inflamed controls (n=12). Computational techniques were utilized for cell segmentation, dimensionality reduction, and cell type clustering to delineate cell populations to analyze cell frequency, marker distribution, and spatial neighborhood. Higher-resolution spatial analysis was conducted using multiplex immunofluorescence.
The results showed a significant increase in neutrophils, effector cytotoxic T cells, and inflammatory macrophages within CD fistula samples compared to CD colitis and control colonic samples. Meanwhile, regulatory T cells showed a decrease. Notably, neutrophils in CD fistulas expressed higher matrix metalloproteinase 9 (MMP9) levels, suggesting involvement in extracellular matrix remodeling. Spatial neighborhood analysis revealed a robust correlation between MMP9+ neutrophils and effector cytotoxic T cells in CD fistulas and colitis samples.
Investigators identified MMP9+ neutrophils in CD fistulas for the first time, linked them to matrix breakdown, and suggested new therapeutic targets.
Source: academic.oup.com/ecco-jcc/advance-article-abstract/doi/10.1093/ecco-jcc/jjae033/7625300
