The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease.
The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease.
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角膜上皮来源的血小板反应蛋白-1 在干眼病中的免疫调节作用
DOI：
10.1016/j.jtos.2018.07.005
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Dana R
中科院分区：
文献类型：
--
作者：
Tan X;Chen Y;Foulsham W;Amouzegar A;Inomata T;Liu Y;Chauhan SK;Dana R
在这项研究中，我们研究了角膜上皮源性血栓反应蛋白-1(TSP-1)在干眼病(DED)小鼠模型中的表达及其免疫调节功能。用受控环境舱(CEC)诱导雌性C57BL/6小鼠发生DED，共14天。用实时荧光定量聚合酶链式反应和流式细胞仪检测角膜上皮细胞TSP-1mRNA和蛋白表达。将幼龄和DED小鼠的角膜上皮细胞与骨髓来源的树突状细胞(BMDCs)在干扰素γ作用下培养48h，用流式细胞仪检测BMDC表面MHC-II和CD86的表达。然后，将重组TSP-1或抗TSP-1抗体加入到共培养中，检测上述激活标志物的BMDC表达。最后，用重组TSP-1或人血清白蛋白(HSA)局部治疗DED小鼠，观察角膜DC的成熟度、炎症细胞因子的表达和DED的严重程度。DED患者角膜上皮细胞TSP-1mRNA表达上调。与野生型小鼠相比，DED小鼠角膜上皮细胞抑制BMDC表达MHC-II和CD86的能力增强，这种作用可被TSP-1阻断并被重组TSP-1增强。最后，局部应用重组TSP-1显著抑制了DED小鼠角膜DC的成熟和促炎细胞因子的mRNA表达，并改善了疾病的严重程度。我们的研究阐明了上皮源性TSP-1在抑制DC成熟中的作用，并显示了其在DED中限制角膜上皮病变的翻译潜力。
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). 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 naïve or DED mice were cultured with bone marrow derived dendritic cells (BMDCs) in the presence of IFNγ for 48 hours, 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. 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. 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.
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