ILC3-to-ILC1 transition is strongly supported in Crohn's Disease but evidence for UC plasticity is limitedImmune Cell Changes May Offer New Paths for Crohn's Disease

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a group of chronic gastrointestinal inflammatory diseases characterized by persistent mucosal inflammation and intestinal immune barrier dysfunction. Innate lymphoid cells (ILCs) are key regulators of mucosal immunity; however, the contribution of their context-dependent plasticity to IBD-associated immune barrier remodeling remains incompletely defined. This narrative review summarizes the intestinal distribution and functional specialization of ILC subsets, their dysregulation in the IBD microenvironment, and the molecular signals that regulate ILC plasticity. Current evidence most strongly supports an ILC3-to-ILC1 transition in CD, whereas direct evidence for defined directional ILC plasticity in UC and for ILC2 lineage conversion in intestinal IBD remains limited. We also discuss the context-dependent roles of ILC2s in epithelial repair, inflammation, and fibrosis, as well as the functional reprogramming of ILC3s from barrier-protective to potentially pathogenic states. In addition, this review summarizes the cytokine, transcriptional, epigenetic, and metabolic mechanisms associated with ILC fate remodeling and discusses potential therapeutic strategies targeting these pathways. Overall, ILC plasticity may represent a disease- and tissue-specific mechanism contributing to intestinal immune barrier remodeling, although its causal role and therapeutic relevance require further validation in human IBD. These findings provide a framework for developing more precisely stratified and context-dependent therapeutic approaches for IBD.