Roles for specialized secretory epithelial cells in inflammatory bowel disease.

PURPOSE OF REVIEW: Current inflammatory bowel disease (IBD) therapies mainly target immune pathways, yet many patients fail to achieve durable remission, highlighting the need to understand epithelial-intrinsic drivers of chronic inflammation and barrier defects. Recent single-cell, spatial, and functional studies have redefined secretory epithelial lineages as active regulators of mucosal immunity, microbial containment, and tissue recovery.

RECENT FINDINGS: Goblet cells are increasingly recognized as heterogeneous barrier sentinels whose region-specific alterations in mucus organization, microbial sensing, and stress responses can influence disease location and variability. Tuft cells are chemosensory hubs that connect luminal cues to type-2 and neuroimmune circuits, with evidence linking tuft-cell programs to repair-associated remodeling in inflammatory settings. Paneth cell dysfunction in ileal Crohn's disease frequently reflects disrupted antimicrobial and stress-adaptation programs, while colonic ulcerative colitis can exhibit injury-associated Paneth-like remodeling within the regenerative epithelium.

SUMMARY: Secretory epithelial lineages actively regulate mucosal immunity and barrier integrity through region-dependent programs that shift during chronic inflammation. Defining these lineage states and their signaling outputs can improve patient stratification and reveal epithelial-targeted therapeutic strategies that complement immunomodulatory treatment.