Department of Pediatrics, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, 430060, China.
Department of Burn, Wuhan Third Hospital, No.241 Pengliuyang Road, Wuhan, 430060, China.
Clin Exp Med. 2021 Aug;21(3):429-437. doi: 10.1007/s10238-021-00701-3. Epub 2021 Mar 29.
Imbalanced Th17/Treg ratio is implicated in the pathogenesis of aplastic anemia. Studies have indicated that bone marrow-derived mesenchymal stem cells-derived exosomes (BMSC-Exo) could correct imbalanced Th17/Treg in aplastic anemia, but the mechanism remains not fully understand. This study was designed to investigate whether BMSC-Exo regulates the Th17/Treg balance in aplastic anemia by transferring miR-23a-3p. Here, miR-23a-3p inhibitor was utilized to knockdown the expression of miR-23a-3p in BMSC-Exo. A co-culture system of CD4 T cells from aplastic anemia patients and BMSC-Exo was used to explore the effects of BMSC-Exo on the Th17/Treg balance and the underlying mechanism in aplastic anemia. The patients with aplastic anemia exhibited Th17/Treg imbalance favoring the Th17 cells. BMSC-Exo could balance the percentage of Th17 and Treg cells in aplastic anemia, but the effects of BMSC-Exo can be eliminated when miR-23a-3p expression was silenced in BMSCs. IL-6 was a direct target of miR-23a-3p. IL-6 overexpression could abrogate BMSC-Exo-induced balance in Th17/Treg ratio. Overall, BMSC-Exo could balance Th17/Treg ratio in aplastic anemia via suppressing IL-6 expression by transferring miR-23a-3p at least in part. These data indicated miR-23a-3p may be a potential target for the treatment of aplastic anemia. Our study may provide a new idea for the therapy of the disease.
Th17/Treg 失衡与再生障碍性贫血的发病机制有关。研究表明，骨髓间充质干细胞衍生的外泌体（BMSC-Exo）可纠正再生障碍性贫血中的 Th17/Treg 失衡，但机制尚不完全清楚。本研究旨在探讨 BMSC-Exo 是否通过转移 miR-23a-3p 来调节再生障碍性贫血中的 Th17/Treg 平衡。在此，利用 miR-23a-3p 抑制剂敲低 BMSC-Exo 中 miR-23a-3p 的表达。采用再生障碍性贫血患者 CD4 T 细胞与 BMSC-Exo 的共培养系统，探讨 BMSC-Exo 对再生障碍性贫血中 Th17/Treg 平衡的影响及其潜在机制。再生障碍性贫血患者表现出有利于 Th17 细胞的 Th17/Treg 失衡。BMSC-Exo 可平衡再生障碍性贫血中 Th17 和 Treg 细胞的比例，但当沉默 BMSCs 中的 miR-23a-3p 表达时，BMSC-Exo 的作用可以消除。IL-6 是 miR-23a-3p 的直接靶标。过表达 IL-6 可消除 BMSC-Exo 诱导的 Th17/Treg 比值平衡。总之，BMSC-Exo 至少部分通过转移 miR-23a-3p 抑制 IL-6 表达来平衡再生障碍性贫血中的 Th17/Treg 比值。这些数据表明，miR-23a-3p 可能是治疗再生障碍性贫血的潜在靶点。我们的研究可能为该疾病的治疗提供新的思路。
