Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China.
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China.
Biomed Res Int. 2021 Aug 30;2021:5574282. doi: 10.1155/2021/5574282. eCollection 2021.
Programmed cell death 1 ligand (PD-L1) and its receptor (PD-1) are key molecules for immunoregulation and immunotherapy. PD-L1 binding PD-1 is an effective way to regulate T or B cell immunity in autoimmune diseases such as rheumatoid arthritis (RA). In our study, we overexpressed PD-L1 by constructing a recombinant of PD-L1-lentiviral vector, which was subsequently used to transfect mouse bone marrow mesenchymal stem cells (MBMMSCs) and significantly suppressed the development of collagen-induced arthritis (CIA) in DBA/1j mice. In addition, PD-L1-transfected MBMMSCs (PD-L1-MBMMSCs) ameliorated joint damage, reduced proinflammatory cytokine expression, and inhibited T and B cell activation. Furthermore, PD-L1-MBMMSCs decreased the number of dendritic cells and increased the numbers of regulatory T cells and regulatory B cells in joints of CIA mice. In conclusion, our results provided a potential therapeutic strategy for RA treatment with PD-L1-MBMMSC-targeted therapy.
程序性细胞死亡蛋白 1 配体（PD-L1）及其受体（PD-1）是免疫调节和免疫治疗的关键分子。PD-L1 结合 PD-1 是调节类风湿关节炎（RA）等自身免疫性疾病中 T 或 B 细胞免疫的有效方法。在我们的研究中，我们通过构建 PD-L1 慢病毒载体的重组体来过表达 PD-L1，随后用其转染小鼠骨髓间充质干细胞（MBMMSCs），显著抑制 DBA/1j 小鼠胶原诱导性关节炎（CIA）的发展。此外，转染 PD-L1 的 MBMMSCs（PD-L1-MBMMSCs）改善了关节损伤，降低了促炎细胞因子的表达，并抑制了 T 和 B 细胞的激活。此外，PD-L1-MBMMSCs 减少了 CIA 小鼠关节中的树突状细胞数量，增加了调节性 T 细胞和调节性 B 细胞的数量。总之，我们的结果为使用 PD-L1-MBMMSC 靶向治疗治疗 RA 提供了一种潜在的治疗策略。
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