Na Hyemin, Im Keon-Il, Kim Nayoun, Lee Junseok, Gil Sojin, Min Gi-June, Cho Seok-Goo
Institute for Translational Research and Molecular Imaging, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
iScience. 2024 Apr 18;27(5):109783. doi: 10.1016/j.isci.2024.109783. eCollection 2024 May 17.
Human bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been proposed as a treatment for graft-versus-host disease (GVHD), which is a major complication following allogeneic hematopoietic cell transplantation. However, clinical trials have not yielded good results, and human decidua-derived mesenchymal stromal cells (DSCs) have been proposed as an alternative. In addition, the mechanism by which DSCs exert their immunomodulatory effects is still unknown. We found that knockdown of IL-6 in DSCs reduced the expression of PD-L1 and PD-L2, which are known as classical immune checkpoint inhibitors. Expression of PD-L1 and PD-L2 was restored by adding recombinant IL-6 to the DSCs. When DSCs and IL-6-knockdown DSCs were administered as treatment in a murine GVHD model, the group receiving IL-6-knockdown DSCs had significantly higher mortality and clinical scores compared to the group receiving DSCs. Taken together, these data suggest that the IL-6 signaling pathway is a crucial contributor to the immunosuppressive capacity of DSCs.
人骨髓间充质基质细胞（BM-MSCs）已被提议用于治疗移植物抗宿主病（GVHD），这是异基因造血细胞移植后的一种主要并发症。然而，临床试验并未取得良好效果，人蜕膜间充质基质细胞（DSCs）已被提议作为替代方案。此外，DSCs发挥其免疫调节作用的机制仍不清楚。我们发现，敲低DSCs中的IL-6可降低PD-L1和PD-L2的表达，这两种蛋白是已知的经典免疫检查点抑制剂。通过向DSCs中添加重组IL-6可恢复PD-L1和PD-L2的表达。当将DSCs和IL-6敲低的DSCs作为治疗药物施用于小鼠GVHD模型时，与接受DSCs的组相比，接受IL-6敲低DSCs的组死亡率和临床评分显著更高。综上所述，这些数据表明IL-6信号通路是DSCs免疫抑制能力的关键贡献因素。
