Myeloid derived suppressor cells (MDSCs) are a heterogenous population of immature hematopoietic precursors with known immunoregulatory functions. The immunosuppressive role of MDSCs has been highlighted in several inflammatory ophthalmic disorders; however, their therapeutic application in suppressing the immune-mediated changes in dry eye disease (DED) has not been studied. We observed significant reduction in antigen presenting cell (APC) frequencies and their maturation in the presence of MDSCs. Moreover, co-culturing MDSCs with T helper 17 cells (Th17) resulted in reduced Th17 frequencies and their IL-17 expression. On the contrary, MDSCs maintained regulatory T cell frequencies and enhanced their function in-vitro. Furthermore, we delineated the role of interleukin-10 (IL-10) secreted by MDSCs in their immunoregulatory functions. We confirmed these results by flow cytometry analysis and observed that treatment with MDSCs in DED mice effectively suppressed the maturation of APCs, pathogenic Th17 response, and maintained Treg function and significantly ameliorated the disease. The results in this study highlight the potential therapeutic application of MDSCs in treating refractory DED.

中文翻译：

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局部施用髓源性抑制细胞可预防免疫介导的干眼病的进展

骨髓源性抑制细胞（MDSC）是具有已知免疫调节功能的未成熟造血前体细胞的异质群体。 MDSC 的免疫抑制作用在多种炎症性眼科疾病中得到了凸显。然而，它们在抑制干眼病（DED）免疫介导变化方面的治疗应用尚未得到研究。我们观察到在 MDSC 存在的情况下，抗原呈递细胞 (APC) 频率及其成熟度显着降低。此外，将 MDSC 与辅助性 T 细胞 17 (Th17) 共培养会导致 Th17 频率及其 IL-17 表达降低。相反，MDSC 维持了调节性 T 细胞频率并增强了其体外功能。此外，我们描述了 MDSC 分泌的白细胞介素 10 (IL-10) 在其免疫调节功能中的作用。我们通过流式细胞术分析证实了这些结果，并观察到用 MDSC 治疗 DED 小鼠可有效抑制 APC 的成熟、致病性 Th17 反应，并维持 Treg 功能并显着改善疾病。本研究的结果强调了 MDSC 在治疗难治性 DED 方面的潜在治疗应用。