Single-cell atlas maps Crohn’s disease drivers in ileal tissue

Researchers generated IBDverse, a 1.1‑million‑cell scRNA‑seq atlas of terminal ileal biopsies from 111 Crohn’s disease patients and 232 controls, using discovery and replication cohorts to identify robust cell-type signatures. They map 57 cell clusters across epithelial, immune and mesenchymal compartments, find IFN‑driven MHC‑I upregulation in epithelial cells (persisting in progenitors after inflammation resolves), and identify ITGA4+ macrophages as key inflammatory drivers with enriched JAK–STAT signaling and IL‑6/IL‑12/IL‑23 production. Heritability analyses link inflammatory monocytes and macrophages to CD risk, outlining a cellular–molecular framework with therapeutic implications; data and code are publicly available.