Group 3 innate lymphoid cells (ILC3) have been detected in both murine and human decidual tissues where they are thought to play a relevant role in the induction and maintenance of pregnancy. However, limited information exists on the molecular mechanisms that regulate these cells, including immune checkpoints. Here, we show that ILC3 express the inhibitory checkpoints programmed cell death (PD-1) and T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) during the first trimester of pregnancy and that these receptors could regulate production of cytokines, including IL-22, IL-8, and TNF-α, induced by IL-23. We also show that the intermediate extravillous trophoblast (iEVT) expresses high levels of the PD-1-ligand PD-L1, suggesting that PD-1/PD-L1 interaction may regulate ILC3 function at the feto-maternal interface. Our present data provide the first evidence that human decidual ILC3 express a functional PD-1. It is possible that an altered expression or function of PD-1 may break the immune-tolerance resulting in pregnancy failure.

第 3 组先天性淋巴样细胞 (ILC3) 已在小鼠和人类蜕膜组织中检测到，它们被认为在妊娠的诱导和维持中发挥相关作用。然而，关于调节这些细胞的分子机制（包括免疫检查点）的信息有限。在这里，我们表明 ILC3 在妊娠早期表达抑制性检查点程序性细胞死亡 (PD-1) 和 T 细胞免疫球蛋白和粘蛋白结构域蛋白 3 (TIM-3)，并且这些受体可以调节细胞因子的产生，包括IL-22、IL-8 和 TNF-α，由 IL-23 诱导。我们还表明中间绒毛外滋养细胞 (iEVT) 表达高水平的 PD-1-配体 PD-L1，表明 PD-1/PD-L1 相互作用可能调节胎儿-母体界面的 ILC3 功能。我们目前的数据提供了人类蜕膜 ILC3 表达功能性 PD-1 的第一个证据。PD-1 的表达或功能改变可能会破坏免疫耐受，导致妊娠失败。