Abstract：
We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.
摘要：
我们和其他小组已经证明，系统性红斑狼疮（SLE）患者的骨髓间充质干细胞（BM-MSCs）表现出衰老的迹象，包括调节Treg的能力降低。Treg细胞缺陷或Treg细胞缺乏被认为是SLE进展的重要因素。外泌体,纳米级囊泡，丰富的分子和遗传内容，在细胞间通信中发挥关键作用。本研究的目的是探讨MSCs-外泌体对SLETregs细胞的调控机制,进一步阐明衰老BM-MSCs免疫失调的机制，为SLE治疗的新靶点提供理论依据和数据支持。在研究中,成功分离BM-MSC和外泌体。外泌体可以被初始CD4+T细胞摄取。MSCs-外泌体在体内减弱SLE临床表现，但SLE患者的MSCs-外泌体无效。来自SLE患者的MSC-外泌体在体内和体外失调Treg细胞分化。外泌体miR-20a-5p有助于MSC-外泌体调节Treg细胞的作用。上调miR-20a-5p在SLEMSCs外泌体中的表达可以恢复其促进Treg分化的能力和治疗效果。本研究进一步阐明了BM-MSCs-外泌体在免疫调节机制中的作用,为SLE的非细胞自体移植治疗提供了新思路。
