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Virginia L. Calder, Ifeoma Offiah, Grazyna Galatowicz, Richard Mellors, Margarita Calonge, Michael E. Stern; Conjunctival Expression of Interleukin-17 Receptors in Chronic Allergic Eye Disease: An Immunoregulatory Role for Interleukin-17 on Conjunctival Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6631.
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© ARVO (1962-2015); The Authors (2016-present)
In chronic allergic eye disease (CAED), increased levels of interleukin-(IL)17 producing TH17 cells have been found localized to subepithelial and epithelial layers in conjunctival biopsy tissue specimens. The aim of this study was to investigate the presence of IL-17 in human conjunctival tissues and to examine the effect of IL-17 on conjunctival cell responses in vitro.
Conjunctival biopsy tissue sections from subjects with active CAED (vernal keratoconjunctivitis and atopic keratoconjunctivitis; n = 9), seasonal allergic conjunctivitis (SAC; n =6) and controls (n = 5) were stained for IL-17A expression. SAC (n = 5) and CAED (n = 9) sections were also stained for expression of IL-17 receptors (-RA, -RC). As a model of epithelial cell responses in vitro, human conjunctival epithelial cell line (IOBA) cells were cultured for 24 hrs in supplemented DMEM alone or with: PMA [1ng/ml]; TNF-α [25ng/ml] and IL-1β (10ng/ml); IL-17A (10ng/ml); Zymosan (20µg/ml); Poly I:C (50µg/ml) or LPS (5µg/ml). For IL-17R inhibition, pre-activated IOBA cells were treated with anti-IL-17RA blocking mAb or control Ab for 2 hrs before washing, then IL-17A was added for a further 24 hrs. Production of soluble CD44, IL-8, IL-17A/F and TGF-β1 were assayed by ELISA or multi-cytokine bead arrays.
IL-17A expression was significantly increased in CAED, localized to the conjunctival epithelium (P<0.05) and stromal tissues (P<0.05) as compared to controls. SAC and CAED sections expressed IL-17RA and IL-17RC, the latter being significantly increased in CAED compared to SAC (P<0.01). Conjunctival epithelial cells did not secrete IL-17A or F but did secrete IL-8 and soluble CD44 in response to various stimuli. Following IL-17A exposure and treatment with anti-IL-17RA Ab, there was significant increased IL-8 secretion in cells pre-stimulated with PMA (P=0.05), IL-17A (P=0.03) and poly I:C (P=0.02). In contrast, TGF-β1 was significantly decreased following anti-IL-17RA treatment in response to IL-17A, but only in unstimulated cells.
IL-17-IL-17RA binding downregulated IL-8 and upregulated TGF-β1 production by conjunctival epithelial cells, suggesting a potential modulatory role for IL-17 at the ocular surface.
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