From mucus secretion to immune surveillance: the evolving roles of goblet cells in intestinal homeostasis and inflammation

Background Intestinal goblet cells (GCs) are specialized epithelial cells essential for forming the protective mucus barrier. Recent research has significantly expanded our understanding of their roles beyond mucus secretion, revealing critical functions in immune regulation and mucosal homeostasis. Dysfunction of these cells is implicated in the pathogenesis of intestinal disorders, particularly inflammatory bowel disease (IBD). Scope and methods This review synthesizes the current literature on intestinal GC biology, encompassing their developmental pathways, cellular heterogeneity, and multifaceted functions within the intestinal chemical, mechanical, immune, and biological barriers. Key findings and contribution We highlight the remarkable plasticity and heterogeneity of GCs, detailing newly identified subtypes such as sentinel GCs and intercrypt GCs, and their distinct roles in mucosal defence. The review elucidates how GCs contribute to intestinal homeostasis not only through mucin ( MUC2 ) production but also via antigen sampling, cytokine secretion, and interactions with the commensal microbiota. Furthermore, we consolidate evidence on the signalling pathways and molecular regulators governing GC differentiation and function. Conclusion and implications The dysfunction or depletion of intestinal GCs is a hallmark of IBD, leading to barrier breakdown and sustained inflammation. This review underscores the emerging role of GCs as key guardians of intestinal health and promising therapeutic targets. A deeper understanding of GC biology paves the way for novel strategies aimed at restoring intestinal barrier function in IBD.