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.

骨髓间充质干细胞（BMSCs）与免疫性血小板减少症（ITP）有关，其潜在机制尚未完全阐明。在这里，我们试图研究 BMSC 是否可以通过外泌体途径调节 ITP 中的 Th17/Treg 失衡。我们首先评估了 ITP 患者中 Th17 细胞和 Tregs 的比例，表明 ITP 患者表现出明显的 Th17/Treg 失衡。BMSCs-外泌体的治疗显着降低了 ITP 患者CD4 ⁺ T 细胞中Th17/Treg 的比率。此外，miR-146a-5p 在 BMSCs-外泌体中高度表达。miR-146a-5p在CD4 ^+中表达明显升高BMSCs-外泌体处理后的T细胞。BMSCs-外泌体 miR-146a-5p 沉默促进了 Th17 细胞的比例并抑制了 CD4 ⁺ T 细胞中 Treg 的比例。此外，miR-146a-5p 直接与 IL-1R 相关激酶-1 (IRAK) 相互作用，并抑制 IRAK1 表达。IRAK1 过表达促进了 CD4 ⁺ T 细胞中的Th17/Treg 比率，这被 BMSCs-外泌体 miR-146a-5p 消除。总之，这些发现表明 BMSC 衍生的外泌体 miR-146a-5p 通过抑制 IRAK1 表达来调节 ITP 中的 Th17/Treg 失衡。因此，这项工作表明 BMSCs-外泌体 miR-146a-5p 可能是 ITP 的潜在治疗靶点。