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Nancy Reyes, Tomas Blanco, Rose Mathew, Daniel R Saban; Novel Mouse Model of Severe Ocular Allergy Reveals a Key Role for Pathogenic Th17 Cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4058. doi: https://doi.org/.
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Ocular allergies range from mild (i.e. seasonal and perennial allergic conjunctivitis) to severe (i.e. atopic and vernal keratoconjunctivitis). Current established models of ocular allergy predominantly mimic the mild forms. Our lab has developed a novel mouse model that mimics the severe forms where there is corneal involvement. We hypothesize that T cell subsets—other than Th2—distinguish severe disease from the milder forms of ocular allergy.
The severe model was induced by immunizing C57BL/6 (B6) mice intraperitoneally (IP) with ovalbumin in pertussis toxin and aluminum hydroxide (alum). The mild model was induced by immunizing B6 mice IP with short ragweed pollen in alum. Mice were challenged topically with their respective antigen for 7 days and assessed for clinical signs 20 minutes and 6 hours post-challenge. Lymph nodes, corneas, and conjunctivae were then harvested. Corneas and conjunctivae were assessed for infiltrating leukocytes and lymphocytes assessed for Th1, Th2, and Th17 frequencies via FACS.
Compared to the mice with mild ocular allergies (n=23), mice with severe allergies (n=22) displayed higher clinical scores with sustained allergic symptoms. FACS analysis of the leukocyte infiltrate into the conjunctiva and cornea in the severe model was 5-6 fold higher compared to the mild model. Analysis of lymphocytes by FACS revealed higher Th2 (IL-4, IL-5, IL-13) frequencies in the severe model. Interestingly, the biggest difference between the two models was seen in Th1 (IFN-γ) and Th17 (IL-17) levels, where IL-17 was almost completely absent in the mild model. Further analysis of Th17 cells in the severe model revealed that these IL-17-producing cells co-express IFN-γ, consistent with ‘pathogenic’ Th17 cells.
This is the first described model of ocular allergy that mimics the more severe forms. We can now begin to dissect the pathobiological differences between the mild and severe forms of ocular allergy. Our data suggests that the differences between mild versus severe ocular allergy is due to ‘pathogenic’ Th17 cells (IL-17+IFN-γ+). Further studies are needed to determine if these pathogenic Th17 cells are the main mediators for severe ocular allergy and if targeting them may lead to better therapies.
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