Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia

•Goblet cells are key to maintaining homeostasis in mucosal epithelia. •Goblet cells are more than merely secretory cells. •Genetic regulation of goblet cell function is altered in mucosa-associated diseases. •Insight into goblet cell function may provide novel therapies for mucosal diseases. Many organs throughout the body maintain epithelial homeostasis by employing a mucosal barrier which acts as a lubricant and helps to preserve a near-sterile epithelium. Goblet cells are largely responsible for secreting components of this mucosal barrier and represent a major cellular component of the innate defense system. In this review we summarize what is known about the signaling pathways that control goblet cell differentiation in the intestine, the lung, and the ocular surface, and we discuss a novel functional role for goblet cells in mucosal epithelial immunology. We highlight the cell type-specificity of the circuitry regulating goblet cell differentiation and shed light on how changes to these pathways lead to altered goblet cell function, a prominent feature of mucosa-associated diseases. Many organs throughout the body maintain epithelial homeostasis by employing a mucosal barrier which acts as a lubricant and helps to preserve a near-sterile epithelium. Goblet cells are largely responsible for secreting components of this mucosal barrier and represent a major cellular component of the innate defense system. In this review we summarize what is known about the signaling pathways that control goblet cell differentiation in the intestine, the lung, and the ocular surface, and we discuss a novel functional role for goblet cells in mucosal epithelial immunology. We highlight the cell type-specificity of the circuitry regulating goblet cell differentiation and shed light on how changes to these pathways lead to altered goblet cell function, a prominent feature of mucosa-associated diseases. mechanism of exocytosis in which secreted products bud off in plasma-membrane bound vesicles and are shed into the lumen. the mucosal epithelium lining the inner surface of the eyelid; ‘forniceal’ refers to the folded region near the limbus and ‘palpebral’ refers to the flat region between the fornix and the eyelid epithelium. antigen-presenting cells important in innate and adaptive immunity. the process by which a multipotent stem or progenitor cell becomes restricted in function to become a more specialized cell type. mechanism of releasing secreted contents of a cell into the extracellular environment. process by which the cellular environment is kept stable and constant in response to fluctuating external conditions. the inner space of a cylindrical tube, such as the intestine. abnormal conversion of one mature differentiated cell type into a new differentiated cell type in response to stimuli.