During early pregnancy, decidual NK (dNK) cells play indispensable roles in many processes including the decidualization, the implantation, and the maintenance of immune tolerance. Abnormal cytotoxic activity of NK cells can cause recurrent spontaneous abortion (RSA), while the regulatory mechanism of NK cytotoxicity remains to be unclear. In this study, we found that kynurenine in decidua and villus was in a comparable level between patients with RSA and normal pregnancy women. However, the aryl hydrocarbon receptor (AhR) in decidual NK cells was significantly increased in RSA. Compared with AhR⁻ NK cells, cytotoxic activity-related molecules (NKP30, NKP46, NKG2D, perforin, granzyme B and IFN-γ) was highly expressed in both AhR⁺ peripheral and decidual NK cells, and kynurenine stimulation promoted the expression of killer receptors and the cytoplasmic granules in an AhR-dependent manner. Stimulation with TNF-α, IL-β and LPS upregulated the AhR expression in dNK cells in vitro. These results indicate that kyn/AhR signal enhances the cytotoxicity of NK cells, and increased expression of AhR may be an induction factor of RSA.

在妊娠早期，蜕膜NK（dNK）细胞在蜕膜化、着床和维持免疫耐受等许多过程中发挥着不可或缺的作用。NK细胞的异常细胞毒活性可导致复发性自然流产（RSA），而NK细胞毒作用的调控机制尚不清楚。在这项研究中，我们发现 RSA 患者和正常怀孕妇女的蜕膜和绒毛中的犬尿氨酸水平相当。然而，蜕膜NK细胞中的芳烃受体（AhR）在RSA中显着增加。与 AhR ^- NK 细胞相比，细胞毒活性相关分子（NKP30、NKP46、NKG2D、穿孔素、颗粒酶 B 和 IFN-γ）在两个 AhR ⁺外周和蜕膜 NK 细胞，犬尿氨酸刺激以 AhR 依赖性方式促进杀伤受体和细胞质颗粒的表达。用 TNF-α、IL-β 和 LPS 刺激体外dNK 细胞中的 AhR 表达上调。这些结果表明 kyn/AhR 信号增强了 NK 细胞的细胞毒性，AhR 表达增加可能是 RSA 的诱导因子。