Myeloid-derived suppressor cells shift Th17/Treg ratio and promote systemic lupus erythematosus progression through arginase-1/miR-322-5p/TGF-β pathway
Myeloid-derived suppressor cells shift Th17/Treg ratio and promote systemic lupus erythematosus progression through arginase-1/miR-322-5p/TGF-β pathway
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髓源性抑制细胞通过精氨酸酶-1/miR-322-5p/TGF-β 途径改变 Th17/Treg 比率并促进系统性红斑狼疮进展。
DOI：
10.1042/cs20200799
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发表时间：
2020-08-01
期刊：
影响因子：
6
通讯作者：
Yi, Huanfa
中科院分区：
文献类型：
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作者：
Pang, Bo;Zhen, Yu;Yi, Huanfa
免疫细胞在系统性红斑狼疮（SLE）中发挥重要作用。我们之前发现骨髓源性抑制细胞 (MDSC) 衍生的精氨酸酶-1 (Arg-1) 促进 SLE 中 Th17 细胞的分化。在这项研究中，我们利用 RNA 芯片来识别 MDSC 和 Th17 细胞之间的 microRNA 调控网络。与单独培养的 Th17 细胞相比，小鼠 miR-322-5p 的同源基因在 Th17+MDSC 组中显着上调，而在 Th17+MDSC+Arg-1 抑制剂组中与 Th17+MDSC 组相比下调。我们进一步评估了小鼠中的miR-322-5p和Th17/Treg平衡，发现Th17细胞和Treg的比例均升高，并且miR-322-5p过表达激活了转化生长因子-β途径。此外，尽管 miR-322-5p 表达在 SLE 小鼠中较高，但在用 Arg-1 抑制剂治疗后有所下降。 Th17细胞比例和Th17/Treg比值与miR-322-5p水平相关。总之，MDSC 衍生的 Arg-1 和 mmu-miR-322-5p 不仅能促进 Th17 细胞和 Treg 分化，还能改变 SLE 中 Th17/Treg 的比例。 Arg-1/miR-322-5p 轴可能作为 SLE 的新治疗靶点。
Immune cells play important roles in systemic lupus erythematosus (SLE). We previously found that myeloid-derived suppressor cell (MDSC)-derived arginase-1 (Arg-1) promoted Th17 cell differentiation in SLE. In this study, we performed RNA-chip to identify the microRNA regulation network between MDSCs and Th17 cells. miR-542-5p in humans, as the homologous gene of miR-322-5p in mice was significantly upregulated in the Th17+MDSC group compared to Th17 cells cultured alone and downregulated in the Th17+MDSC+Arg-1 inhibitor group compared to the Th17+MDSC group. We further evaluated the miR-322-5p and Th17/Treg balance in mice and found that the proportions of both Th17 cells and Tregs were elevated and that miR-322-5p overexpression activated the transforming growth factor-β pathway. Moreover, although miR-322-5p expression was higher in SLE mice, it decreased after treatment with an Arg-1 inhibitor. The proportion of Th17 cells and Th17/Treg ratio correlated with miR-322-5p levels. In conclusion, MDSC-derived Arg-1 and mmu-miR-322-5p not only promote Th17 cell and Treg differentiation, but also shift the Th17/Treg ratio in SLE. The Arg-1/miR-322-5p axis may serve as a novel treatment target for SLE.