Natural killer cell-mediated immunopathology in recurrent pregnancy losses

T. Luu, L. Alsubki, Katherine Wolf, Amy Thees, U. Ganieva, S. Dambaeva, K. Beaman, J. Kwak‐Kim
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Abstract

Natural killer (NK) cells have a dual role in human reproduction for maternal-fetal tolerance and protection from infection. During the ovarian cycle and pregnancy, peripheral NK (pNK) and uterine NK (uNK) cells dynamically change their proportions and cytotoxicities to prepare and accommodate invading trophoblast and maintain pregnancy. However, dysregulated pNK and uNK cell proportions and cytotoxic activities have been associated with aberrant spiral artery remodeling and trophoblast invasion, leading to implantation failures and recurrent pregnancy losses (RPLs). This review will focus on the role of NK cells in RPLs reviewing the ontogeny of NK cells, changes in pNK and uNK cell levels, and activities during the ovarian cycle, normal pregnancy, and RPL. In addition, the immunopathological role of NK cells in endometrial/decidual vascular development and killer immunoglobin-like receptor (KIR) and human leukocyte antigen (HLA)-C interactions are discussed.
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自然杀伤细胞介导的免疫病理在复发性妊娠损失
自然杀伤细胞(NK)在人类生殖中具有母婴耐受和保护免受感染的双重作用。在卵巢周期和妊娠期间,外周NK(pNK)和子宫NK(uNK)细胞动态改变其比例和细胞毒性,以准备和适应入侵的滋养层并维持妊娠。然而,pNK和uNK细胞比例失调和细胞毒性活性与异常的螺旋动脉重塑和滋养层侵袭有关,导致植入失败和复发性妊娠损失(RPL)。这篇综述将集中于NK细胞在RPL中的作用,回顾NK细胞的个体发生、pNK和uNK细胞水平的变化以及卵巢周期、正常妊娠和RPL期间的活动。此外,还讨论了NK细胞在子宫内膜/蜕膜血管发育中的免疫病理作用以及杀伤性免疫球蛋白样受体(KIR)和人类白细胞抗原(HLA)-C相互作用。
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