Viganò P, Gaffuri B, Somigliana E, Infantino M, Vignali M, Di Blasio A M
Molecular Biology Laboratory, Istituto Auxologico Italiano, V.le Monte Nero 32, 20135 Milan, Italy.
Mol Hum Reprod. 2001 Oct;7(10):971-7. doi: 10.1093/molehr/7.10.971.
A predominance of T helper (Th)2-type cytokines and a weakening of Th1 responses seem to be critical for the maintenance of a successful gestation. Among Th2-type cytokines, interleukin (IL)-10 is produced by human cytotrophoblasts and defects in this production result in specific pathological conditions of pregnancy. The current opinion is that IL-10 serves to protect the fetus from a harmful maternal immune response. However, production of the cytokine and its direct effect on uterine natural killer (uNK) cells, which represent the predominant lymphocyte population infiltrating the pregnant endometrium, are largely unknown. Thus, to shed light on the cytokine network at the maternal-fetal barrier during early pregnancy, we investigated the IL-10 system in uNK cells. We showed that uNK cells express the mRNA transcripts for IL-10 and IL-10 receptor. Production of IL-10 by the uNK cells was enhanced by both IL-2 and IL-12. Treatment with IL-10 alone enhanced uNK cell cytotoxic activity. In contrast, the cytokine did not modify the basal or stimulated production of interferon (IFN)-gamma by uNK. Thus, IL-10 does not act as a direct antagonist of uNK cell function and activation. However, IL-10 produced by uNK cells in response to IL-12 and IL-2 may still have a feedback inhibitory effect on the production of deleterious cytokines within the uterine microenvironment.
辅助性T(Th)2型细胞因子占优势以及Th1反应减弱似乎对维持成功妊娠至关重要。在Th2型细胞因子中,白细胞介素(IL)-10由人细胞滋养层细胞产生,该细胞因子产生缺陷会导致特定的妊娠病理状况。目前的观点认为,IL-10有助于保护胎儿免受有害的母体免疫反应影响。然而,该细胞因子的产生及其对子宫自然杀伤(uNK)细胞的直接作用在很大程度上尚不清楚,uNK细胞是浸润妊娠子宫内膜的主要淋巴细胞群体。因此,为了阐明妊娠早期母胎屏障处的细胞因子网络,我们研究了uNK细胞中的IL-10系统。我们发现uNK细胞表达IL-10及其受体的mRNA转录本。IL-2和IL-12均可增强uNK细胞产生IL-10。单独用IL-10处理可增强uNK细胞的细胞毒性活性。相反,该细胞因子不会改变uNK细胞基础状态下或受刺激时产生干扰素(IFN)-γ的情况。因此,IL-10并非uNK细胞功能和激活的直接拮抗剂。然而,uNK细胞在响应IL-12和IL-2时产生的IL-10可能仍对子宫微环境中有害细胞因子的产生具有反馈抑制作用。