Department of Immunology, Binzhou Medical University, Yantai, Shandong Province 264003, People's Republic of China.
Department of Anatomy, Binzhou Medical University, Yantai, Shandong Province 264003, People's Republic of China.
Cell Immunol. 2020 Jun;352:104113. doi: 10.1016/j.cellimm.2020.104113. Epub 2020 Apr 13.
Human placenta-derived mesenchymal stromal cells (hPMSCs) are promising candidates for the treatment of graft-versus-host disease (GVHD), which is associated with high IL-1β levels. In this study, the effects of IL-1β and hPMSCs on each other were investigated by analyzing the proportion of Th1, Th2 and CD4IL-10 T cells and PD-L1 expression, as well as the adhesion, migration, and proliferation of hPMSCs. The results showed that hPMSCs decreased IL-1β levels and downregulated Th1/Th2 and Th1/CD4IL-10 T cells ratios in the GVHD model. The in vitro results revealed that IL-1β strengthened the hPMSCs capacity to reduce the Th1/Th2 and Th1/CD4IL-10 T cell ratios, inhibited the adhesion and proliferation of hPMSCs and increased PD-L1 expression on hPMSCs via the JAK and NF-κB pathways. Overall, these findings suggested that hPMSCs alleviate GVHD by decreasing IL-1β level and maintaining the balance among different T cell subsets. IL-1β enhanced the ability of hPMSCs to balance different T cell subsets and inhibited hPMSCs adhesion and proliferation by regulating PD-L1 expression via the JAK and NF-κB pathways.
人胎盘间充质基质细胞(hPMSCs)是治疗移植物抗宿主病(GVHD)的有前途的候选物,GVHD 与高水平的 IL-1β 相关。在这项研究中,通过分析 Th1、Th2 和 CD4IL-10 T 细胞的比例以及 PD-L1 表达,以及 hPMSCs 的黏附、迁移和增殖,研究了 IL-1β 和 hPMSCs 之间的相互作用。结果表明,hPMSCs 降低了 GVHD 模型中的 IL-1β 水平,并下调了 Th1/Th2 和 Th1/CD4IL-10 T 细胞的比例。体外结果表明,IL-1β 通过 JAK 和 NF-κB 通路增强了 hPMSCs 降低 Th1/Th2 和 Th1/CD4IL-10 T 细胞比例的能力,抑制了 hPMSCs 的黏附和增殖,并增加了 hPMSCs 上的 PD-L1 表达。总的来说,这些发现表明,hPMSCs 通过降低 IL-1β 水平并维持不同 T 细胞亚群之间的平衡来缓解 GVHD。IL-1β 通过调节 PD-L1 表达,通过 JAK 和 NF-κB 通路增强了 hPMSCs 平衡不同 T 细胞亚群的能力,并抑制了 hPMSCs 的黏附和增殖。