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Exosomes derived from mesenchymal stem cells regulate Treg/Th17 balance in aplastic anemia by transferring miR-23a-3p

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Abstract

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.

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The data could be obtained upon request to the corresponding author.

Abbreviations

AA:

Aplastic anemia

BMSCs:

Bone marrow-derived MSCs

IL:

Interleukin

miRNAs:

MicroRNAs

MSCs:

Mesenchymal stem cells

TGF-β1:

Transforming growth factor-β1; Th1: T helper type 1

Treg:

Regulatory T

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Authors and Affiliations

  1. Department of Pediatrics, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, 430060, China

    Qing-zhao Shi, Hong-mei Yu, Miao Liu & Xue Cheng

  2. Department of Burn, Wuhan Third Hospital, No.241 Pengliuyang Road, Wuhan, 430060, China

    Hong-mei Chen

Authors
  1. Qing-zhao Shi
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  2. Hong-mei Yu
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  3. Hong-mei Chen
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  4. Miao Liu
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  5. Xue Cheng
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Contributions

Q-Z Shi designed the study; Q-Z Shi, H-M Yu, H-M Chen, M Liu, and X Cheng conducted the experiments and analyzed the data; Q-Z Shi drafted the paper; and all authors reviewed and approved the paper.

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Correspondence to Qing-zhao Shi.

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This study was approved by the Ethics Committee of Renmin Hospital of Wuhan University.

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Shi, Qz., Yu, Hm., Chen, Hm. et al. Exosomes derived from mesenchymal stem cells regulate Treg/Th17 balance in aplastic anemia by transferring miR-23a-3p. Clin Exp Med 21, 429–437 (2021). https://doi.org/10.1007/s10238-021-00701-3

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  • DOI: https://doi.org/10.1007/s10238-021-00701-3

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