Andreescu Mihaela, Frîncu Francesca, Plotogea Mihaela, Mehedințu Claudia
Department of Clinical Sciences, Hematology, Faculty of Medicine, Titu Maiorescu University of Bucharest, 040051 Bucharest, Romania.
Department of Hematology, Colentina Clinical Hospital, 020125 Bucharest, Romania.
J Clin Med. 2023 Feb 8;12(4):1355. doi: 10.3390/jcm12041355.
Immune tolerance at the feto-maternal interface is crucial for the growth of the semi-allograft fetus in the womb. The outcome of pregnancy is dependent on a fine balance between various immunological forces. For a long time, the potential role of the immune system in pregnancy disorders has remained enigmatic. Current evidence has revealed that natural killer (NK) cells are the predominant immune cell population in the uterine decidua. NK cells cooperate with T-cells to provide an optimal microenvironment for the growth of the developing fetus by producing cytokines, chemokines, and angiogenic factors. These factors support trophoblast migration and angiogenesis which regulates the process of placentation. NK cells differentiate between "self" and "non-self" through their surface receptors known as killer-cell immunoglobulin-like receptors (KIRs). They induce immune tolerance through communication via their KIR and fetal human leucocyte antigens (HLA). KIRs are surface receptors of NKs that comprise both activating and inhibiting receptors. Due to the wide diversity manifested by its genes, the KIR repertoire is different in each individual. Significant evidence has implicated KIRs in recurrent spontaneous abortion (RSA); however, maternal KIR gene diversity in RSA is still unclear. Research has shown that immunological aberrancies including activating KIRs, NK abnormalities, and T cell downregulation are risk factors for RSA. In this review, we discuss relevant data from experimental studies on NK cell abnormalities, KIR, and T-cells in the incidence of recurrent spontaneous abortion.
母胎界面的免疫耐受对于子宫内半同种异体胎儿的生长至关重要。妊娠结局取决于各种免疫力量之间的精细平衡。长期以来，免疫系统在妊娠疾病中的潜在作用一直不明确。目前的证据表明，自然杀伤（NK）细胞是子宫蜕膜中主要的免疫细胞群体。NK细胞与T细胞协作，通过产生细胞因子、趋化因子和血管生成因子，为发育中的胎儿生长提供最佳微环境。这些因子支持滋养层迁移和血管生成，从而调节胎盘形成过程。NK细胞通过其表面受体（称为杀伤细胞免疫球蛋白样受体，KIRs）区分“自身”和“非自身”。它们通过KIR与胎儿人类白细胞抗原（HLA）之间的通讯诱导免疫耐受。KIRs是NK细胞的表面受体，包括激活受体和抑制受体。由于其基因表现出广泛的多样性，每个个体的KIR库都不同。大量证据表明KIRs与复发性自然流产（RSA）有关；然而，RSA中母体KIR基因多样性仍不清楚。研究表明，包括激活KIRs、NK细胞异常和T细胞下调在内的免疫异常是RSA的危险因素。在这篇综述中，我们讨论了关于NK细胞异常、KIR和T细胞在复发性自然流产发生率方面的实验研究的相关数据。
