Different fibroblast subtypes propel spatially defined ileal inflammation through TNFR1 signalling in murine ileitis.

ABSTRACT: Crohn's disease (CD) is a persistent inflammatory disorder primarily affecting the terminal ileum. The Tnf^ΔΑRE mice, which spontaneously develop CD-like ileitis due to TNF overexpression, represent a faithful model of the human disease. Here, via single-cell RNA sequencing in Tnf^ΔΑRE mice, we show that murine TNF-dependent ileitis is characterized by cell expansion in tertiary lymphoid organs (TLO), T cell effector reprogramming, and accumulation of activated macrophages in the submucosal granulomas. Within the stromal cell compartment, fibroblast subsets (telocytes, trophocytes, Pdgfra^loCd81^- cells) are less abundant while lymphatic endothelial cells (LEC) and fibroblastic reticular cells (FRC) show relative expansion compared to the wild type.

SUBMITTER: Iliopoulou L 

PROVIDER: S-EPMC11953319 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature