Decidual NK cells (dNK) are the mos

Decidual NK cells (dNK) are the most abundant maternal leukocytes in the decidua, especially in the first trimester, making up 70% of the maternal CD45+ leukocyte population. (48) The dNK cells are distinct from majority of peripheral blood NK cells, in that they are large, granular, and are CD56hi and CD16− (8). The origin of these cells is unclear, although some have proposed possible recruitment of a subset of peripheral blood CD56hi NK cells into the decidua (49). Interestingly, during early pregnancy, dNK accumulate as a dense infiltrate around the trophoblast cells, but they progressively decrease in number from mid-gestation onward (50). This timing seems to implicate that dNK cells may be involved in modulating trophoblast invasion and vascular remodeling. Indeed, dNK have been shown to produce vascular endothelial growth factor C (VEGFC), placental growth factor (PIGF), and angiopoietin 2 (ANG2).

Decidual NK cells may also be important in modulating the degree of trophoblast invasion, as they are seen in close proximity to the invading trophoblasts in the decidua. Certainly, dNK have been shown to express killer inhibitory receptor (KIR) (51), CD94/NKG2A (52), and ILT2 (53), which recognize HLA-C and HLA-G, respectively, expressed on trophoblast cells. The HLA-C–KIR interaction is thought to be important in the pathogenesis of pre-eclampsia. As HLA-C is dimorphic and KIR polymorphic, it has been shown that certain combinations of maternal KIR and fetal HLA-C lead to an increased risk of pre-eclampsia, possibly through modulation of trophoblast migration, implying that HLA-C–KIR interaction is important in placentation (54, 55). However, NK cell KIR and HLA-C mismatch clearly does not explain all cases of pre-eclampsia, since only 30% of pre-eclamptic pregnancies have the at-risk maternal KIR phenotype (KIR AA) (54). HLA-G–ILT2 interaction on NK cells on the other hand, has been shown to increase dNK secretion of inflammatory and proangiogenic factors such as IL-1β, IL-6, TNF, and IL-8 (56). NK cells themselves are also susceptible to modulation by the decidual cytokine milieu. Indeed, dNK cells are thought to be the mediator of fetal demise in IL-10-deficient mice treated with LPS, which conversely can be rescued by administration of IL-10 (57). This suggests that IL-10 may modulate dNK cell cytotoxicity.

Collectively, these data suggest that dNK cells are important for modulation of trophoblast invasion and decidual vascularization in pregnancy. However, the recognition and tolerance of paternal allo-antigens via APC presentation during pregnancy, clearly requires the participation of other limbs of the immune system, such as the adaptive immune cells.

結果 (中文) 1:

蜕膜 NK 细胞 (丹麦) 是最丰富的产妇白细胞蜕膜组织，尤其是在第一孕期，弥补产妇 CD45 + 白细胞人口的 70%。(48) 丹麦细胞外周血 NK 细胞，绝大多数的区别是，他们都大，颗粒状，，是 CD56hi 和 CD16− (8)。这些细胞的起源是子集的不清楚，虽然有些建议可能招聘的蜕膜 (49) 外周血 CD56hi NK 细胞。有趣的是，妊娠早期，丹麦积累作为滋养层细胞，周围密集渗透但他们逐步从妊娠中期前进 (50) 的数量在减少。这个时机似乎牵连到那丹麦细胞可能参与调节滋养细胞浸润及血管重塑。事实上，丹麦已经产生血管内皮生长因子 C (VEGFC)、 胎盘生长因子 (PIGF) 和促血管生成素 2 (ANG2)。Decidual NK cells may also be important in modulating the degree of trophoblast invasion, as they are seen in close proximity to the invading trophoblasts in the decidua. Certainly, dNK have been shown to express killer inhibitory receptor (KIR) (51), CD94/NKG2A (52), and ILT2 (53), which recognize HLA-C and HLA-G, respectively, expressed on trophoblast cells. The HLA-C–KIR interaction is thought to be important in the pathogenesis of pre-eclampsia. As HLA-C is dimorphic and KIR polymorphic, it has been shown that certain combinations of maternal KIR and fetal HLA-C lead to an increased risk of pre-eclampsia, possibly through modulation of trophoblast migration, implying that HLA-C–KIR interaction is important in placentation (54, 55). However, NK cell KIR and HLA-C mismatch clearly does not explain all cases of pre-eclampsia, since only 30% of pre-eclamptic pregnancies have the at-risk maternal KIR phenotype (KIR AA) (54). HLA-G–ILT2 interaction on NK cells on the other hand, has been shown to increase dNK secretion of inflammatory and proangiogenic factors such as IL-1β, IL-6, TNF, and IL-8 (56). NK cells themselves are also susceptible to modulation by the decidual cytokine milieu. Indeed, dNK cells are thought to be the mediator of fetal demise in IL-10-deficient mice treated with LPS, which conversely can be rescued by administration of IL-10 (57). This suggests that IL-10 may modulate dNK cell cytotoxicity.Collectively, these data suggest that dNK cells are important for modulation of trophoblast invasion and decidual vascularization in pregnancy. However, the recognition and tolerance of paternal allo-antigens via APC presentation during pregnancy, clearly requires the participation of other limbs of the immune system, such as the adaptive immune cells.

結果 (中文) 3:

蜕膜NK细胞（DNK）是最丰富的母体蜕膜细胞，尤其是在孕早期，由母体CD45白细胞总数的70%。（48）dNK细胞不同于外周血NK细胞占多数，因为他们是大，颗粒，和CD56hi和CD16−（8）。这些细胞的起源尚不清楚，虽然有人提出可能的招聘外周血NK细胞的一个子集的CD56hi到蜕膜组织（49）。有趣的是，在怀孕早期，DNK积累为致密浸润在滋养层细胞逐渐减少，但他们的数量从孕中期开始（50）。这个时机似乎暗示dNK细胞可能参与调节滋养细胞浸润和血管重塑。的确，DNK产生血管内皮生长因子C（VEGF-C），胎盘生长因子（PIGF），和血管生成素2（Ang2）。

蜕膜NK细胞也可能是重要的调节滋养细胞浸润的程度，当他们看到在靠近入侵的滋养层细胞在蜕膜。当然，DNK已表现出杀伤抑制受体（KIR）（51），CD94/NKG2A（52），和（53），识别ILT2 HLA-C和HLA-G，分别，在滋养细胞中表达。HLA-C–KIR的相互作用被认为在子痫前期的发病机制非常重要。由于是双和HLA-C KIR多态性，结果表明，母体KIR与胎儿HLA-C的某些组合导致子痫前期的风险增加，可能通过调节滋养层细胞的迁移，这意味着HLA-C–KIR的相互作用是非常重要的胎盘（54，55）。然而，NK细胞KIR和HLA-C配显然不能解释所有病例的先兆子痫，因为只有30%的先兆子痫孕妇有高危产妇KIR表型（KIR AA）（54）。HLA-G–ILT2互动对NK细胞，另一方面，已被证明能增加血管炎症，如IL-1，IL-6，TNF因子β，DNK分泌IL-8，和（56）。NK细胞本身也由蜕膜细胞因子环境容易调制。确实dNK细胞被认为是胎儿死亡在体内LPS处理小鼠的中介，这反过来可以通过管理IL-10获救（57）。这表明，IL-10可调节蜕膜细胞的细胞毒性。

总的来说，这些数据表明，dNK细胞为滋养细胞侵入蜕膜血管和妊娠期重要的调节。不过识别和异体抗原的耐受性通过APC递呈的父亲怀孕期间，显然需要免疫系统的其他肢体的参与，如免疫细胞。