@article {1323942,
	title = {The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease},
	journal = {Ocul Surf},
	volume = {16},
	number = {4},
	year = {2018},
	month = {2018 Oct},
	pages = {470-477},
	abstract = {PURPOSE: In this study, we examine the expression of corneal epithelium-derived thrombospondin-1 (TSP-1) and its immunomodulatory functions in a validated murine model of dry eye disease (DED). METHODS: DED was induced in female C57BL/6 using a controlled environment chamber (CEC) for 14 days. mRNA and protein expression of TSP-1 by corneal epithelial cells was quantified using real-time PCR and flow cytometry. Corneal epithelial cells from either na{\"\i}ve or DED mice were cultured with bone marrow derived dendritic cells (BMDCs) in the presence of IFNγ for 48 h, and BMDC expression of MHC-II and CD86 was determined using flow cytometry. Next, either recombinant TSP-1 or anti-TSP-1 antibody was added to the co-culture, and BMDC expression of above activation markers was evaluated. Finally, either DED mice were topically treated with either recombinant TSP-1 or human serum albumin (HSA), and maturation of corneal DCs, expression of inflammatory cytokines, and DED severity were investigated. RESULTS: mRNA expression of TSP-1 by the corneal epithelium was upregulated in DED. Corneal epithelial cells derived from mice with DED demonstrated an enhanced capacity in suppressing BMDC expression of MHC-II and CD86 relative to wild type mice, and this effect was abrogated by TSP-1 blockade and potentiated by recombinant TSP-1. Finally, topical application of recombinant TSP-1 significantly suppressed corneal DC maturation and mRNA expression of pro-inflammatory cytokines, and ameliorated disease severity in mice with DED. CONCLUSIONS: Our study elucidates the function of epithelium-derived TSP-1 in inhibiting DC maturation and shows its translational potential to limit corneal epitheliopathy in DED.},
	issn = {1937-5913},
	doi = {10.1016/j.jtos.2018.07.005},
	author = {Tan, Xuhua and Chen, Yihe and Foulsham, William and Amouzegar, Afsaneh and Inomata, Takenori and Liu, Yizhi and Chauhan, Sunil K and Dana, Reza}
}
