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Co-expression of NKp46 with activating or inhibitory receptors on, and cytokine production by, uterine endometrial NK cells in recurrent pregnancy loss
Journal of Reproductive Immunology ( IF 3.4 ) Pub Date : 2021-04-18 , DOI: 10.1016/j.jri.2021.103324
Ryu Takeyama 1 , Atsushi Fukui 1 , Chuxian Mai 1 , Mayu Yamamoto 1 , Shinichiro Saeki 1 , Ayano Yamaya 1 , Hiroaki Shibahara 1
Affiliation  

NKp46 (CD335) is one of the activating receptors expressed on NK cells and its expression is decreased in patients with reproductive failure. However, the reasons remain unknown. In this study, we aimed to clarify the significance of decreased NKp46 expression in reproductive failure. Uterine endometrial samples collected from 39 patients with recurrent pregnancy loss (RPL) were assigned to high- or low-risk groups based on an 18 % ratio of CD16+/CD56dim NK cells in uterine endometrial NK (uNK) cells. We analyzed the expression of NKp46 and other activating or inhibitory receptors on, and intracellular cytokine production by NK cells using multicolor flow cytometry. The numbers of NKp46+/CD16 NK, NKp46+/NKG2C NK, IL-4+/CD56+ NK, and IL-10+/CD56+ NK cells were significantly decreased, whereas that TNF-α+/CD56+ NK cells was significantly increased in the high-risk group, when compared with the low-risk group (P < 0.05 for all). The ratios of TNF-α/IL-4, IFN-γ/IL4, TNF-α/IL-10, and IFN-γ/IL10 cytokine production in uNK cells were significantly increased in the high-risk when compared with the low-risk group (P < 0.05, for all). It is suggested that low expression of activating receptors on NKp46 uNK cells is more prevalent in high-risk women.



中文翻译:

NKp46 与激活或抑制受体的共表达,以及子宫内膜 NK 细胞在复发性流产中的细胞因子产生

NKp46 (CD335) 是 NK 细胞上表达的激活受体之一,在生殖障碍患者中其表达降低。但是,原因仍然未知。在这项研究中,我们旨在阐明 NKp46 表达降低在生殖失败中的意义。根据子宫内膜 NK (uNK) 细胞中 CD16 + /CD56暗淡NK 细胞的 18% 比率,从 39 名复发性流产 (RPL) 患者收集的子宫内膜样本被分配到高风险组或低风险组。我们使用多色流式细胞术分析了 NKp46 和其他激活或抑制受体的表达,以及 NK 细胞的细胞内细胞因子产生。NKp46 + /CD16 NK、NKp46 + 的数量/NKG2C - NK、IL-4 + /CD56 + NK 和 IL-10 + /CD56 + NK 细胞显着减少,而高危组中 TNF-α + /CD56 + NK 细胞显着增加,当与低风险组相比(所有P < 0.05)。与低危组相比,高危组 uNK 细胞中 TNF-α/IL-4、IFN-γ/IL4、TNF-α/IL-10 和 IFN-γ/IL10 细胞因子产生的比率显着增加。风险组(P < 0.05,对于所有)。这表明 NKp46 uNK 细胞上激活受体的低表达在高危女性中更为普遍。

更新日期:2021-04-27
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