Roles for specialized secretory epithelial cells in inflammatory bowel disease

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.

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.

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.