We previously demonstrated that mesenchymal stem cells (MSCs) ameliorated experimental autoimmune uveoretinitis (EAU) in rats. Recently, MSC-derived exosomes (MSC-Exo) were thought to carry functions of MSCs. In this study, we tested the effect of local administration of human MSC-Exo on established EAU in the same species. Rats with EAU induced by immunization with interphotoreceptor retinol-binding protein 1177-1191 peptide were treated by periocular injections of increasing doses of MSC-Exo starting at the disease onset for 7 consecutive days. The in vitro effects of MSC-Exo on immune cell migration and responder T cell proliferation were examined by chemotactic assays and lymphocyte proliferation assays, respectively. We found that MSC-Exo greatly reduced the intensity of ongoing EAU as their parent cells by reducing the infiltration of T cell subsets, and other inflammatory cells, in the eyes. Furthermore, the chemoattractive effects of CCL2 and CCL21 on inflammatory cells were inhibited by MSC-Exo. However, no inhibitory effect of MSC-Exo on IRBP-specific T cell proliferation was observed. These results suggest that MSC-Exo effectively ameliorate EAU by inhibiting the migration of inflammatory cells, indicating a potential novel therapy of MSC-Exo for uveitis.

中文翻译：

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间充质干细胞衍生的外来体对实验性自身免疫性葡萄膜炎的影响。

我们以前证明了间充质干细胞（MSCs）改善了大鼠实验性自身免疫性葡萄膜视网膜炎（EAU）。近来，认为MSC来源的外来体（MSC-Exo）具有MSC的功能。在这项研究中，我们测试了人类MSC-Exo的局部给药对同一物种中已建立的EAU的影响。从疾病发作开始，通过眼周注射递增剂量的MSC-Exo来治疗用感光细胞间视黄醇结合蛋白1177-1191肽免疫诱导的EAU大鼠。分别通过趋化测定和淋巴细胞增殖测定检查了MSC-Exo对免疫细胞迁移和应答性T细胞增殖的体外作用。我们发现，MSC-Exo通过减少眼睛中T细胞亚群和其他炎性细胞的浸润，大大降低了正在进行的EAU作为其亲代细胞的强度。此外，MSC-Exo抑制了CCL2和CCL21对炎性细胞的化学吸引作用。但是，没有观察到MSC-Exo对IRBP特异性T细胞增殖的抑制作用。这些结果表明，MSC-Exo通过抑制炎性细胞的迁移而有效地改善了EAU，表明MSC-Exo对葡萄膜炎的潜在新疗法。