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大鼠骨髓间充质干细胞对体外 Treg/Th17 免疫平衡的调控作用。

Regulatory effect of rat bone marrow mesenchymal stem cells on Treg/Th17 immune balance in vitro.

机构信息

Department of Transplant Surgery, Tianjin First Central Hospital, Tianjin 300192, P.R. China.

Hillman Center for Pediatric Transplantation, Department of Transplant Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.

出版信息

Mol Med Rep. 2020 May;21(5):2123-2130. doi: 10.3892/mmr.2020.11019. Epub 2020 Mar 11.

Abstract

Bone marrow mesenchymal stem cells (BM‑MSCs) regulate the balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells. However, the role of different factors on BM‑MSCs‑mediated regulation of the Treg/Th17 balance is unknown. BM‑MSCs and CD4+ T lymphocytes were co‑cultured with various treatments. The ratio of Treg/Th17 cells was calculated and the expression of different cytokines was measured. BM‑MSCs were found to have a proliferative effect on Th17 cells at a basal concentration and at a 2‑fold increase in the number of BM‑MSCs. However, when the number of BM‑MSCs used was increased 4‑fold, they had an inhibitory effect on the Th17 cells. The effect of BM‑MSCs on Tregs was inhibited by the addition of tacrolimus but not rapamycin. The effect of BM‑MSCs on Th17 cells was inhibited by rapamycin. Additionally, the effect of BM‑MSCs on Tregs were inhibited by the addition of a transforming growth factor‑β (TGF‑β) blocker, whereas these TGF‑β‑blockers had no effect on Th17 cells. Addition of an interleukin (IL)‑2 blocker reduced the proportion of Th17 cells when co‑cultured with a high number of MSCs compared with the low concentration group and the proportion of Treg cells was significantly decreased when cells were treated with an IL‑2 blocker compared with the control group. Together, these results showed the varying effects of MSCs on the ratio of Treg/Th17, its dependence on the number of MSCs and the effects of cytokines in inducing these changes in the balance.

摘要

骨髓间充质干细胞 (BM-MSCs) 调节调节性 T 细胞 (Treg) 和辅助性 T 细胞 17 (Th17) 细胞之间的平衡。然而,不同因素对 BM-MSCs 介导的 Treg/Th17 平衡调节的作用尚不清楚。将 BM-MSCs 和 CD4+T 淋巴细胞与各种处理方法共培养。计算 Treg/Th17 细胞的比例,并测量不同细胞因子的表达。研究发现,在基础浓度和 BM-MSCs 数量增加 2 倍的情况下,BM-MSCs 对 Th17 细胞具有增殖作用。然而,当使用的 BM-MSCs 数量增加 4 倍时,它们对 Th17 细胞具有抑制作用。添加他克莫司而非雷帕霉素可抑制 BM-MSCs 对 Treg 的作用。雷帕霉素抑制 BM-MSCs 对 Th17 细胞的作用。此外,添加转化生长因子-β (TGF-β) 阻断剂可抑制 BM-MSCs 对 Treg 的作用,而这些 TGF-β 阻断剂对 Th17 细胞没有影响。添加白细胞介素 (IL)-2 阻断剂可降低与高浓度 MSC 共培养时 Th17 细胞的比例,与对照组相比,用 IL-2 阻断剂处理细胞时 Treg 细胞的比例显著降低。总之,这些结果表明 MSC 对 Treg/Th17 比值的影响不同,其依赖于 MSC 的数量,以及细胞因子在诱导这些平衡变化中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0788/7115201/ad9d685ff954/MMR-21-05-2123-g00.jpg

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