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.