The intestinal barrier is a complex structure that allows absorption of nutrients while ensuring protection against intestinal pathogens and a balanced immunity. Development and maintenance of a functional intestinal barrier is a multifactorial process, which is only partially understood. Here we review novel findings on the emerging role of mesenchymal cells in this process using insights gained from lineage tracing approaches, Cre-based genes deletion and single cells transcriptomics. The current evidence points toward a key organizer role for distinct mesenchymal lineages in intestinal development and homeostasis, regulating both epithelial and immune components of the intestinal barrier. We further discuss recent findings on functional mesenchymal heterogeneity and implications for intestinal regeneration and inflammatory intestinal pathologies.
Mucosal Immunology, 2023.