Immune–epithelial coordination of barrier repair in inflammatory bowel disease: from cell survival to functional healing

Epithelial repair in inflammatory bowel disease involves preservation of viable cells, coverage of wounds, renewal of epithelial populations and recovery of selective transport and secretion. These processes overlap, yet improvement in one does not establish completion of the others. This narrative review examines how immune signals influence these transitions and how experimental repair findings relate to patient outcomes. We first describe the junctional and mucus barrier and the distinction between physiological, endoscopic and histological measurements. We then examine epithelial death control, regenerative pathways and immune-derived signals using studies selected for compartment-specific perturbation, functional measurements or informative discrepancies between experimental and clinical findings. Interleukin-22 illustrates the importance of context: it promotes regeneration in several experimental systems, disrupts barrier function in a human colon chip, and has not yielded demonstrated efficacy as efmarodocokin alfa in a phase II ulcerative colitis trial. In one small infliximab study, paired measurements from nine patients showed an increase in epithelial resistance after treatment. Larger controlled studies are needed to establish how consistently functional recovery accompanies immune control. We organize the evidence around target engagement, epithelial response, barrier function and patient benefit, with example assays and common interpretive pitfalls for each. The resulting synthesis identifies the measurements needed to distinguish protection from repair and to test whether an epithelial effect adds value to effective immune therapy. Clinical studies must ultimately establish that a specified functional improvement is durable and beneficial to patients.