Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands.
Mildred Clinics Arnhem, Arnhem, Netherlands.
Front Immunol. 2024 Mar 20;15:1353556. doi: 10.3389/fimmu.2024.1353556. eCollection 2024.
Natural killer (NK) cells, with a unique NK cell receptor phenotype, are abundantly present in the non-pregnant (endometrium) and pregnant (decidua) humanuterine mucosa. It is hypothesized that NK cells in the endometrium are precursors for decidual NK cells present during pregnancy. Microenvironmental changes can alter the phenotype of NK cells, but it is unclear whether decidual NK cell precursors in the endometrium alter their NK cell receptor repertoire under the influence of pregnancy. To examine whether decidual NK cell precursors reveal phenotypic modifications upon pregnancy, we immunophenotyped the NK cell receptor repertoire of both endometrial and early-pregnancy decidual NK cells using flow cytometry. We showed that NK cells in pre-pregnancy endometrium have a different phenotypic composition compared to NK cells in early-pregnancy decidua. The frequency of killer-immunoglobulin-like receptor (KIR expressing NK cells, especially KIR2DS1, KIR2DL2L3S2, and KIR2DL2S2 was significantly lower in decidua, while the frequency of NK cells expressing activating receptors NKG2D, NKp30, NKp46, and CD244 was significantly higher compared to endometrium. Furthermore, co-expression patterns showed a lower frequency of NK cells co-expressing KIR3DL1S1 and KIR2DL2L3S2 in decidua. Our results provide new insights into the adaptations in NK cell receptor repertoire composition that NK cells in the uterine mucosa undergo upon pregnancy.
自然杀伤 (NK) 细胞具有独特的 NK 细胞受体表型,大量存在于非妊娠(子宫内膜)和妊娠(蜕膜)的人子宫黏膜中。据推测,子宫内膜中的 NK 细胞是妊娠期间存在的蜕膜 NK 细胞的前体。微环境的变化可以改变 NK 细胞的表型,但尚不清楚子宫内膜中的蜕膜 NK 细胞前体是否会在妊娠的影响下改变其 NK 细胞受体库。为了研究蜕膜 NK 细胞前体是否会在妊娠时表现出表型改变,我们使用流式细胞术免疫表型分析了子宫内膜和早孕蜕膜 NK 细胞的 NK 细胞受体库。结果表明,与早孕蜕膜 NK 细胞相比,妊娠前子宫内膜 NK 细胞具有不同的表型组成。与子宫内膜相比,妊娠蜕膜中表达杀伤免疫球蛋白样受体 (KIR) 的 NK 细胞,尤其是 KIR2DS1、KIR2DL2L3S2 和 KIR2DL2S2 的频率明显降低,而表达激活受体 NKG2D、NKp30、NKp46 和 CD244 的 NK 细胞的频率明显升高。此外,共表达模式显示,妊娠蜕膜中 KIR3DL1S1 和 KIR2DL2L3S2 共表达的 NK 细胞频率较低。我们的研究结果为 NK 细胞在子宫黏膜中受妊娠影响而发生的 NK 细胞受体库组成适应性改变提供了新的见解。