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Bone marrow mesenchymal stem cell-derived exosomes induce the Th17/Treg imbalance in immune thrombocytopenia through miR-146a-5p/IRAK1 axis

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Abstract

Bone marrow mesenchymal stem cells (BMSCs) are associated with immune thrombocytopenia (ITP), the underlying mechanism has not been fully elucidated. Here, we attempted to investigate whether BMSCs can regulate Th17/Treg imbalance in ITP through the exosome pathway. We first assessed the proportions of Th17 cells and Tregs in ITP patients, showing that ITP patients exhibited an evident imbalance of Th17/Treg. BMSCs-exosomes’ treatment significantly reduced Th17/Treg ratio in the CD4+ T cells of ITP patients. Moreover, miR-146a-5p was highly expressed in BMSCs-exosomes. The expression of miR-146a-5p was obviously increased in CD4+ T cells following the treatment of BMSCs-exosomes. BMSCs-exosomal miR-146a-5p silencing promoted the proportions of Th17 cells and repressed the proportions of Tregs in CD4+ T cells. In addition, miR-146a-5p directly interacted with IL-1R-associated kinase-1 (IRAK), and repressed IRAK1 expression. IRAK1 overexpression promoted Th17/Treg ratio in CD4+ T cells, which was abolished by BMSCs-exosomal miR-146a-5p. In conclusion, these findings demonstrate that BMSC-derived exosomal miR-146a-5p regulates Th17/Treg imbalance in ITP by repressing IRAK1 expression. Thus, this work suggests that BMSCs-exosomal miR-146a-5p may be a potential therapeutic target for ITP.

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Funding

This work was supported by the National Natural Science Foundation of China (NFSC 81460037) and Postgraduate Innovation Special Fund of Jiangxi Province (YC2020-B031).

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, 33000, Jiangxi, China

    Yue He, Dexiang Ji, Wei Lu, Fei Li, Xianbao Huang, Ruibin Huang & Guoan Chen

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  1. Yue He
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Correspondence to Guoan Chen.

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13577_2021_547_MOESM1_ESM.tif

Supplementary file1 (TIF 338 KB) Supplementary figure 1 BMSCs-exosomes had no effect on Th17/Treg ratio in CD4+ T cells of healthy individuals. CD4+ T cells were isolated from peripheral blood of healthy individuals. CD4+ T cells were incubated with BMSCs-exosomes or PBS. Normal CD4+ T cells served as control. (A-D) Flow cytometry was performed to assess the proportions of Th17 cells and Tregs in the CD4+ T cells. (E-G) ELISA was performed to examine the concentrations of IL-17, IL-10 and TGF-β in the CD4+ T cells. N = 3.

13577_2021_547_MOESM2_ESM.tif

Supplementary file2 (TIF 131 KB) Supplementary figure 2 The expression of IRAK1 in CD4+ T cells. CD4+ T cells were transfected with pcDNA3.1-IRAK1 or pcDNA3.1-NC. The expression of IRAK1 in CD4+ T cells was assessed by WB. N = 3. **P < 0.01 vs. Vector.

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He, Y., Ji, D., Lu, W. et al. Bone marrow mesenchymal stem cell-derived exosomes induce the Th17/Treg imbalance in immune thrombocytopenia through miR-146a-5p/IRAK1 axis. Human Cell 34, 1360–1374 (2021). https://doi.org/10.1007/s13577-021-00547-7

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