Abstract：
Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (BMSC-Exos) have a variety of biological functions and are extensively involved in the regulation of inflammatory diseases, as well as tissue repair and regeneration. However, the mechanism of action of these compounds in dry eye disease (DED) in mice is still unclear. This study demonstrated that the Treg/Th17 ratio was strongly imbalanced in DED clinical samples. BMSC-Exos can modulate the Treg/Th17 balance, improve the integrity of the corneal epithelial layer, and ameliorate DED progression in mice. Mechanistically, BMSC-Exos dramatically decreased the levels of IL-17 and IL-22; increased the levels of IL-4, IL-10, and TGF-β1; and increased tear secretion and the number of goblet cells in the conjunctiva in mice, thus alleviating the progression of DED. This effect is achieved by BMSC-Exos through the delivery of miR-21-5p to target and restrain TLR4, thereby restraining the MyD88/NF-κB pathway. Our study showed that the upregulation of miR-21-5p in BMSC-Exos may be a therapeutic target for DED. These findings support new ideas and a basis for treating DED, as well as for further study of the application value of exosomes in alleviating DED.
摘要：
骨髓间充质干细胞（BMSC）来源的外泌体（BMSC-Exos）具有多种生物学功能，广泛参与炎症性疾病的调节，以及组织修复和再生。然而,这些化合物在小鼠干眼病（DED）中的作用机制尚不清楚。该研究表明,在DED临床样品中Treg/Th17比率强烈不平衡。BMSC-Exos可以调节Treg/Th17平衡，改善角膜上皮层的完整性，并改善小鼠的DED进展。机械上,BMSC-Exos显着降低IL-17和IL-22的水平；增加IL-4，IL-10和TGF-β1的水平；并增加泪液分泌和结膜杯状细胞的数量，从而缓解DED的进展。BMSC-Exos通过将miR-21-5p递送至靶并抑制TLR4,从而抑制MyD88/NF-κB通路来实现这一效果。我们的研究表明，miR-21-5p在BMSC-Exos中的上调可能是DED的治疗靶标。这些发现支持新的想法和治疗DED的基础，以及进一步研究外泌体在缓解DED中的应用价值。
