Elucidating the role of IgA plasma cells and PECAM1-CD38 interaction in intestinal fibrosis: a single-cell RNA sequencing analysis in Crohn's disease.

Abstract

Background: Intestinal fibrosis-associated stricture is a frequent complication of inflammatory bowel disease (IBD), often necessitating endoscopic or surgical interventions. This study aims to investigate the pathogenesis of fibrosis in Crohn's disease (CD), a type of IBD, by analyzing single-cell RNA sequencing (scRNA-Seq) data from colon biopsies of both CD and ulcerative colitis (UC) patients.

Results: The analysis revealed significant cellular heterogeneity, altered cell-cell interactions, and key molecular pathways in both CD and UC. CD showed a marked increase in IgA plasma cells. Ligand-receptor analysis indicated that IgA plasma cells strongly interacted with inflammation-associated fibroblasts (IAFs) in CD, predominantly through the PECAM1-CD38 axis, whereas these interactions were less pronounced in UC. Our study indicated that IL-1β was upregulated in Th17 cells in CD. MAPK signaling pathway were upregulated in Th17 cells.

Conclusions: These findings may provide new insights into the mechanisms underlying early intestinal fibrosis in CD by identifying critical cell types and molecular players. Nonetheless, these observations are exploratory and will require validation in future experiments.