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Michael E. Stern, Christopher S. Schaumburg, Jianping Gao, Anh V. Duong, Annie M. Ratanapinta, Virginia L. Calder, Larry A. Wheeler, Jerry Y. Niederkorn, Stephen C. Pflugfelder, Argyrios N. Theofilopoulos; Plasmacytoid Dendritic Cells are Modulated During the Immunopathogenesis of Desiccating Stress-Induced Experimental Dry Eye. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2327.
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Plasmacytoid dendritic cells (pDC) and derivative type I interferons (IFN-α/β) are important mediators of antiviral immunity. However, type I interferons are also expressed in a variety of autoimmune diseases. Therefore, pDCs were evaluated during the immunopathogenesis of experimental Dry Eye.
Female C57BL/6 wild type mice were exposed to desiccating environmental stress (DS; subcutaneous scopolamine injections; humidity <40%; sustained air flow) for 10 days. A combination of flow cytometry, immunohistochemistry and ELISA were used to phenotype pDCs and IFN-α/β within the draining cervical lymph nodes (CLN) and ocular surface tissues over the course of disease.
Flow cytometric analysis showed elevated frequency of CD11cloPDCA+ pDCs within the draining CLN of Dry Eye mice at day 1 (5.1±1.3%; p=0.04), day 3 (3.1±0.4%; p=0.05), day 5 (5.4±1.0%; p=0.005) and day 10 (4.9±1.8%) compared to naïve control mice (2.2±0.2%). The frequency of CD11cloPDCA+ pDCs was also increased within the ocular surface tissues by day 1 following exposure to DS (6.5±0.1% versus 1.2±0.4%; p=0.0001). Indeed, the higher frequency of pDCs within the CLN correlated with enhanced IFN-α levels by day 1 (2.4±1.2 pg/μg of total protein; p=0.056) and day 5 (3.3±1.4 pg/μg of total protein; p=0.04) of DS relative to control (0.2±1.2 pg/μg of total protein). IFN-α was also increased in the tears of mice with Dry Eye by day 5 of DS (586±57 pg/ml versus 452±35 pg/ml; p=0.03).
Collectively, these data indicate that pDC are modulated during the development of DS-induced Dry Eye disease.
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