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Xiaofen Zheng, Cintia S. de Paiva, De-Quan Li, William J. Farley, Stephen C. Pflugfelder; Desiccating Stress Promotion of Th17 Differentiation by Ocular Surface Tissues through a Dendritic Cell-Mediated Pathway. Invest. Ophthalmol. Vis. Sci. 2010;51(6):3083-3091. doi: 10.1167/iovs.09-3838.
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To explore the phenomenon that corneal and conjunctival tissues subjected to desiccating stress (DS) promote Th17 differentiation by stimulating the production of Th17-inducing cytokines through a dendritic cell (DC)–mediated pathway.
Experimental dry eye was created by subjecting C57BL/6 mice to desiccating environmental stress. Corneal and conjunctival explants from dry eye or control mice were cocultured with DCs for 24 hours before CD4+ T cells were added for an additional 4 to 7 days. Expression of Th17-associated genes in the cornea, conjunctiva, DCs, and CD4+ T cells was evaluated by real-time PCR. Cytokine concentrations in coculture supernatants were measured by immunobead assay. IL-17–producing T cells were identified by ELISPOT bioassay.
Higher levels of IL-17A, TGF-β1, TGF-β2, IL-6, IL-23, and IL-1β mRNA transcripts and TGF-β1, IL-6, and IL-1β protein were observed in corneal epithelium and conjunctiva from dry eye mice. DCs cocultured with epithelial explants from dry eye mice for 2 days produced higher levels of TGF-β1, IL-6, IL-23, and IL-1β mRNA transcripts and of TGF-β1, IL-6, and IL-1β protein. CD4+ T cells cocultured with DCs and epithelial explants from dry eye mice expressed increased levels of IL-17A, IL-17F, IL-22, CCL-20, and retinoic acid receptor–related orphan receptor-γt mRNA transcripts and increased IL-17A protein and number of IL-17–producing T cells (Th17 cells).
These findings demonstrate that DS creates an environment on the ocular surface that stimulates the production of Th17-inducing cytokines by corneal and conjunctival epithelia that promote Th17 differentiation through a dendritic cell–mediated pathway.
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