Ocular surface inflammation associated with Sj？gren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sj？gren’s syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-α and IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage. 1. Introduction Mucin-secreting goblet cells are widely distributed throughout mammalian mucosal surfaces, such as the gastrointestinal, urogenital, and respiratory tracts, where they play a key role in hydrating, lubricating, and clearing pathogens from the underlying epithelium [1]. The importance of goblet cells as major producers of mucins is well established, with critical emphasis placed on the number of functional goblet cells and on the amount and rate at which they synthesize mucins. In fact, alterations in goblet cell numbers and mucin secretion are prominent features of mucosa associated diseases, with increased goblet cell numbers and hypersecretion in conditions such as asthma or cystic fibrosis [2, 3], and mucin depletion and diminished goblet cell density in intestinal diseases such as inflammatory bowel disease or ulcerative colitis [4, 5]. In the eye, goblet cells are the principal secretory cell in the conjunctival epithelium, where they function in lubricating the ocular surface epithelia during the blink response stabilizing the tear film, and as a physical barrier to pathogen penetration [6]. Alterations in goblet cell secretion lead to an unstable tear film and a vulnerable
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