Yuan Bo, Wang Yajie, Chu Yanhua, Yuan Xiaoyong
School of Medicine, Nankai University, Tianjin, China.
Aier Eye Hospital, Tianjin University, Tianjin, China.
BMC Ophthalmol. 2025 Apr 2;25(1):165. doi: 10.1186/s12886-025-04014-x.
Eyes are recognized as immunological privileged site. However, the onset of autoimmune uveitis (AU) prompts an influx of dendritic cells (DCs) into the retinas, tasked with presenting auto-antigens, thereby exacerbating the inflammatory response. Monocyte-derived DCs (moDCs) implicated in various autoimmune disorders, but their specific involvement in AU remains unclear. This study aims to investigate the constitution and dynamics of retinal DCs subsequent to the induction of experimental autoimmune uveitis (EAU).
In our study, an EAU model was established in C57BL/6J mice, and prednisolone acetate (PA) eye drops were administrated unilaterally to the right eye from 5 days post-immunization (dpi). The infiltration of Gr-1CD115CD11cMHC-II cells (monocytes), Gr-1CD115CD11cMHC-II cells (moDCs) and Gr-1CD115CD11cMHC-II cells (conventional dendritic cells, cDCs) within retina were detected by flow cytometry and immunofluorescence stain at 7, 10, 13, and 16 dpi. Additionally, the protein expression and mRNA expression of pivotal cytokines associated with moDCs and inflammation were analysed by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively.
Our findings unveiled a notable rise in moDCs infiltration and differentiation from 7 to 13 dpi. The administration of PA eye drops did not yield a significant variance in either the quantity or the differentiation rate of moDCs. Throughout the initial stages of EAU, the expression of GM-CSF remained consistent, while TGF-β1 exhibited a sustained increase until 13 dpi in the control group and until 10 dpi following PA treatment. Anti-inflammatory cytokines Il-10 and Il-4 displayed no significant increase until 16 dpi after PA administration.
Our results indicate that moDCs exhibited an earlier and more substantial infiltration into the inflamed retina compared to cDCs. This heightened presence of moDCs appeared to play a dominant role in the presentation of auto-antigens during the initial stages of EAU, consequently contributing to the exaggerated autoimmune response within the ocular milieu. The administration of PA exhibited no discernible impact on either the differentiation or the infiltration of moDCs.
眼睛被认为是免疫赦免部位。然而，自身免疫性葡萄膜炎（AU）的发作促使树突状细胞（DCs）涌入视网膜，其任务是呈递自身抗原，从而加剧炎症反应。单核细胞衍生的DCs（moDCs）与多种自身免疫性疾病有关，但其在AU中的具体作用仍不清楚。本研究旨在探讨实验性自身免疫性葡萄膜炎（EAU）诱导后视网膜DCs的组成和动态变化。
在本研究中，在C57BL/6J小鼠中建立EAU模型，并在免疫后5天（dpi）开始对右眼单侧给予醋酸泼尼松龙（PA）滴眼液。在7、10、13和16 dpi通过流式细胞术和免疫荧光染色检测视网膜内Gr-1⁺CD115⁻CD11c⁻MHC-II⁺细胞（单核细胞）、Gr-1⁻CD115⁺CD11c⁻MHC-II⁺细胞（moDCs）和Gr-1⁻CD115⁻CD11c⁺MHC-II⁺细胞（传统树突状细胞，cDCs）的浸润情况。此外，分别通过蛋白质印迹法和定量实时聚合酶链反应（qRT-PCR）分析与moDCs和炎症相关的关键细胞因子的蛋白表达和mRNA表达。
我们的研究结果显示，从7到13 dpi，moDCs的浸润和分化显著增加。PA滴眼液的使用在moDCs的数量或分化率方面均未产生显著差异。在EAU的初始阶段，GM-CSF的表达保持一致，而对照组中TGF-β1持续增加直至13 dpi，PA治疗组则直至10 dpi。抗炎细胞因子Il-10和Il-4在PA给药后直到16 dpi才出现显著增加。
我们的结果表明，与cDCs相比，moDCs在炎症视网膜中的浸润更早且更显著。在EAU的初始阶段，moDCs的这种增加似乎在自身抗原呈递中起主导作用，从而导致眼内环境中自身免疫反应的加剧。PA的使用对moDCs的分化或浸润没有明显影响。
