Sex-dependent differential increase of specialized pro-resolving mediators in extracellular vesicles secreted by human primary conjunctival goblet cells during allergic inflammation.

AIMS: Conjunctival epithelium lines the inside of the eyelids and covers the sclera, thus providing stability to the eye surface. Goblet cells in conjunctival epithelium (CjGCs) are well known for their mucin-secretion function, which wet and protect the ocular surface, but other aspects are still not well understood. To expand our understanding beyond their mucin-secreting function, we investigated CjGC-secreted extracellular vesicles (EVs) and lipid mediators therein. MATERIALS AND METHODS: Using histamine-mediated allergic inflammation in human primary CjGCs (HCjGCs) as a disease model, we quantified using ELISA a proinflammatory mediator PGE2 and two specialized pro-resolving mediators (SPMs) LXA4 and RvD1 in EVs secreted during allergic inflammation. KEY FINDINGS: At 18 h post histamine stimulation, the amount of LXA4 and RvD1 in EVs was notably higher compared to those in unstimulated. Interestingly, this increase was only observed in female EVs but not in males. The mean fold increase of LXA4 and RvD1 in female EVs was 3.9 and 3.4, respectively, but it was only 0.9 and 1.0 in male EVs. Supplying docosahexaenoic acid (DHA, the source of RvD1 and other SPMs) to the culture medium during the allergic inflammation resulted in even higher mean fold increase of 5.3 and 6.9 for LXA4 and RvD1 in female EVs, respectively, but it was only 0.5 and 0.8 in male EVs. SIGNIFICANCE: We conclude that HCjGCs show a clear sex difference in allergic response. Our results may also provide a new insight into the male predisposition to severe forms of allergic conjunctivitis and potential improvement in disease care in the clinic.