Department of Ophthalmology, Nara Medical University, Nara, Japan.
Department of Internal Medicine I, Kansai Medical University, Osaka, Japan.
Invest Ophthalmol Vis Sci. 2018 Jul 2;59(8):3269-3277. doi: 10.1167/iovs.17-22550.
The immune system plays a major role in the pathogenesis of dry eye diseases (DED), and dendritic cells (DCs) are known to be important initiators of acquired immunity. Thus, the purpose of this study was to determine the contribution of DCs to the development of DED.
Mouse dry eye model was induced by subcutaneous injections of scopolamine and was euthanized at the baseline, and 2, 4, and 7 days postinjection. The activation of the DCs was determined by the mixed leukocyte reaction (MLR), and the number of activated CD86+ DCs in the lymph nodes was determined by flow cytometry. Upregulation of cytokines in the culture supernatant of MLR was determined by ELISA.
Significantly increased superficial corneal punctate lesions and decreased number of goblet cells in the conjunctiva were observed in scopolamine-injected mice. The number of activated CD86+ DCs was significantly increased in the cervical lymph nodes but not in the inguinal lymph nodes of the dry eye mice. The stimulatory activity of the DCs derived from the cervical lymph nodes of dry eye mice was significantly higher than that of control mice, and upregulations of IL-17, IL-2, and IL-4 were observed in the culture supernatant of MLR. These results indicate that the DCs of the cervical lymph nodes were activated by the scopolamine injections.
Our results indicate that DCs in our dry eye model were sufficiently activated to stimulate the T cells that participate in the onset and progression of DED.
免疫系统在干眼病（DED）的发病机制中起着重要作用，已知树突状细胞（DC）是获得性免疫的重要启动者。因此，本研究旨在确定 DC 对 DED 发展的贡献。
通过皮下注射东莨菪碱诱导小鼠干眼模型，并在基线、注射后 2、4 和 7 天处死。通过混合淋巴细胞反应（MLR）测定 DC 的激活，通过流式细胞术测定淋巴结中激活的 CD86+ DC 的数量。通过 ELISA 测定 MLR 培养上清液中细胞因子的上调。
在东莨菪碱注射的小鼠中，明显观察到角膜浅层点状病变增加和结膜杯状细胞数量减少。干眼小鼠颈淋巴结中激活的 CD86+ DC 数量明显增加，但腹股沟淋巴结中无明显增加。来自干眼小鼠颈淋巴结的 DC 的刺激活性明显高于对照小鼠，并且在 MLR 的培养上清液中观察到 IL-17、IL-2 和 IL-4 的上调。这些结果表明，颈淋巴结中的 DC 被东莨菪碱注射激活。
我们的结果表明，我们的干眼模型中的 DC 被充分激活，足以刺激参与 DED 发病和进展的 T 细胞。
