Hu Xiaohui, Lai Siying, Liao Aihua
Institute of Reproductive Health and Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Semin Immunopathol. 2025 May 2;47(1):26. doi: 10.1007/s00281-025-01051-y.
A successful pregnancy relies on the precise regulation of the maternal immune system to recognize and tolerate the allogeneic fetus, while simultaneously preventing infection. Immune checkpoint molecules (ICMs), such as programmed death receptor 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T cell immunoglobulin, and mucin-domain containing-3 (Tim-3), play critical roles in regulating the immune response during pregnancy. Emerging research highlights the therapeutic potential of targeting these molecules to restore the immune balance in complicated pregnancies. Understanding the dynamic regulation of ICMs during pregnancy may provide new insights into the pathogenesis of these conditions and offer novel approaches for clinical interventions. Here, we review the expression patterns and functions of key ICMs at the maternal-fetal interface, and their involvement in maintaining immune tolerance throughout gestation. Additionally, we describe the current understanding of immune checkpoint pathways in the pathogenesis of complicated pregnancies and discuss the potential for therapeutic targeting of these pathways in this setting.
成功的妊娠依赖于母体免疫系统的精确调节，以识别和耐受异基因胎儿，同时预防感染。免疫检查点分子（ICM），如程序性死亡受体1（PD-1）、细胞毒性T淋巴细胞抗原4（CTLA-4）、T细胞免疫球蛋白和含粘蛋白结构域3（Tim-3），在调节孕期免疫反应中起关键作用。新兴研究强调了靶向这些分子以恢复复杂妊娠中免疫平衡的治疗潜力。了解孕期ICM的动态调节可能为这些病症的发病机制提供新见解，并为临床干预提供新方法。在此，我们综述了关键ICM在母胎界面的表达模式和功能，以及它们在整个妊娠期维持免疫耐受中的作用。此外，我们描述了目前对复杂妊娠发病机制中免疫检查点途径的理解，并讨论了在此背景下对这些途径进行治疗性靶向的潜力。
