Goblet cell heterogeneity and plasticity in ulcerative colitis: implications for mucus barrier reconstitution

The mucus barrier maintained by intestinal goblet cells is critical for colonic homeostasis, and its disruption is a key pathological hallmark of ulcerative colitis (UC). Goblet cells, once thought to be a homogeneous population of passive mucin secretors, are now recognized as a heterogeneous group composed of functionally specialized subtypes, which including classical secretory, intercrypt, immune sentinel, and Paneth-goblet hybrid phenotypes, each of which contributes uniquely to barrier integrity and immune surveillance. This review thoroughly examines the embryonic origins, molecular regulation, and exceptional flexibility of goblet cells, which allows for dynamic adaptation to microenvironmental inputs. Importantly, we demonstrate the translational potential of goblet cell-centric therapies for restoring mucosal homeostasis and improving long-term outcomes in UC.