Department of Ophthalmology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
ViGenCell Inc., Seoul, Republic of Korea.
Invest Ophthalmol Vis Sci. 2023 Oct 3;64(13):39. doi: 10.1167/iovs.64.13.39.
To evaluate the immune regulatory effect of human cord blood myeloid-derived suppressor cells (MDSCs) in experimental autoimmune uveitis (EAU) models.
MDSCs (1 × 106) or PBS were injected into established C57BL/6 EAU mice via the subconjunctival route on days 0 and 7. The severity of intraocular inflammation was evaluated for up to 3 weeks. Tissue injury and inflammation were analyzed using immunolabelled staining, real-time PCR, and ELISA. In addition, immune cells in draining lymph nodes (LNs) were quantified using flow cytometry.
After 21 days, the clinical scores and histopathological grades of EAU were lower in the MDSCs group compared with the PBS group. Local administration of MDSCs suppressed the oxidative stress and the expression of TNF-α and IL-1β in the retinal tissues. In addition, it inhibited the activation of pathogenic T helper 1 (Th1) and Th17 cells in draining LNs. MDSCs increased the frequency of CD25+ Foxp3+ regulatory T cells and the mRNA expression of IL-10, as an immune modulator.
MDSCs suppressed inflammation and oxidative stress in the retina and inhibited pathogenic T cells in the LNs in EAU. Therefore, ocular administration of MDSCs has therapeutic potential for uveitis.
评估人脐血髓系来源抑制细胞（MDSCs）在实验性自身免疫性葡萄膜炎（EAU）模型中的免疫调节作用。
在第 0 天和第 7 天，通过结膜下途径向已建立的 C57BL/6 EAU 小鼠中注射 MDSCs（1×106）或 PBS。在长达 3 周的时间内评估眼内炎症的严重程度。使用免疫标记染色、实时 PCR 和 ELISA 分析组织损伤和炎症。此外，使用流式细胞术定量引流淋巴结（LN）中的免疫细胞。
21 天后，MDSCs 组的临床评分和 EAU 的组织病理学分级均低于 PBS 组。MDSCs 的局部给药抑制了视网膜组织中的氧化应激和 TNF-α 和 IL-1β 的表达。此外，它抑制了引流 LN 中致病性辅助性 T 细胞 1（Th1）和 Th17 细胞的激活。MDSCs 增加了 CD25+Foxp3+调节性 T 细胞的频率和作为免疫调节剂的 IL-10 的 mRNA 表达。
MDSCs 抑制了 EAU 视网膜中的炎症和氧化应激，并抑制了 LN 中的致病性 T 细胞。因此，眼部给予 MDSCs 具有治疗葡萄膜炎的潜力。
