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Nancy Reyes, Daniel Saban; Central role for Th17 cells and IL-23 in a mouse model of severe allergic eye disease. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5873.
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The pathogenic role for Th17 cells and their pathogenicity through IL-23 ligation in chronic inflammatory disease is now firmly established; however, whether this branch of immunity directly contributes to allergic eye disease is not unknown. Our lab has established a novel mouse model of severe allergic eye disease (AED) and has previously shown that pathogenic Th17 cells (i.e. IFN-γ+IL-17+) arise in these mice. With this in mind, we sought to better characterize the severe clinical manifestations in AED and whether these features are affected by inhibiting the IL-23/IL-17 axis.
AED was induced in C57BL/6 mice by intraperitoneally (IP) injection with ovalbumin (OVA) in pertussis toxin and aluminum hydroxide. After 14 days, mice were challenged topically with OVA for 7 days and examined daily at 20 min and 6 hr post-challenge. Mice were assessed for clinical signs (i.e. chemosis, lid edema, tearing, and redness) and severe clinical manifestations (i.e. corneal opacity, thick mucoid discharge, meibomian gland dysfunction (MGD), and anterior blepharitis). Lymph nodes and conjunctivae were then harvested after the last challenge, and analyzed by flow cytometry. For anti-IL-23 treatment, mice were IP injected with 100 μg of anti-IL-23 three times a week beginning the day before immunization and stopped the day of OVA challenge. Statistical analysis was tested by Student's t-test or Chi-square test. P values <0.05 were considered significant (*).
Results demonstrated that unlike no treatment controls, mice treated with anti-IL-23 displayed reduced clinical signs (*). More importantly, they had reduced development of the severe clinical manifestations seen in untreated controls, specifically: corneal opacity (~12% v. ~0%), thick mucoid discharge (~75% v. ~15%*), meibomian gland dysfunction (~80% v. ~30%*), and anterior blepharitis (~50% v. ~0%*). Anti-IL-23 treatment also resulted in a reduction (*) in Th17 cells and consequent polymorphonuclear leukocyte (PMN) infiltration (CD45+Ly6G+) into the conjunctiva.
We have identified key severe clinical manifestations in AED, which are similar to those seen in patients with atopic and vernal keratoconjunctivitis. Furthermore, pathogenic Th17 cells contribute to the onset of these severe clinical manifestations, and this may be mediated by recruited PMN. Further studies are needed to dissect this mechanism.
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