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J. El Annan, T. Ecoiffier, G. J. Freeman, A. Sharpe, R. Dana; Programmed Death-Ligand 1 (PD-L1) Down-Regulation in Corneal Epithelial Cells: A Potential Role in Mediating Dry Eye-Associated Inflammation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2317.
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The cornea is the most significant target tissue for dry eye syndrome (DES). However, very little is known about the molecular mechanisms of corneal inflammation. Of particular interest is the fact that the cornea appears to be resistant to T cell infiltration in DES. PD-L1 is an important ‘negative’ or inhibitory regulator of immune responses that has been implicated in peripheral tolerance, and is constitutively expressed at high levels by corneal epithelial cells. Our purpose was to study the expression and function of PD-L1 in dry eye syndrome.
Dry eye was induced in female wild type C57BL/6 and C57BL/6 PDL1 KO mice by exposure to a desiccating environment (relative humidity (RH) =22 ± 5%, airflow (AF) =15 l/min, temperature (T) = 21-23 oC) and to systemic scopolamine. Age- and sex-matched control mice were kept in a normal environment (RH =50-70%, no AF, T =21-23 oC) with no administration of scopolamine. Scanning laser confocal microscopy was used to evaluate corneal infiltration of CD3+ T cells after immunohistochemical staining. Corneal epithelial expression of PD-L1 was determined by quantitative real-time PCR.
A significant increase (113%) was seen in the number of T cells in the corneal periphery of PD-L1 KO dry eye mice as compared to wild type dry eye mice and non-dry mice (P<0.05). Decreased expression of PD-L1 was detected in the corneal epithelium of dry eye wild type mice by RT-PCR as compared to non-dry eye mice.
Our data demonstrate that PD-L1 down-regulation in the corneal epithelium of wild type mice after dry eye induction and that there is enhanced T cell infiltration in PD-L1 KO with DES. These findings suggest that down-regulation PDL1 may play an important role in the initiation of corneal inflammation that occurs in dry eye.
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