Department of Medical Biology and Central Electron Microscope Laboratory, Medical School, Pécs University, Pécs, Hungary.
János Szentágothai Research Centre, Pécs University, Pécs, Hungary.
Front Immunol. 2018 Dec 13;9:2890. doi: 10.3389/fimmu.2018.02890. eCollection 2018.
Pregnancy represents a unique immunological situation. Though paternal antigens expressed by the conceptus are recognized by the immune system of the mother, the immune response does not harm the fetus. Progesterone and a progesterone induced protein; PIBF are important players in re-adjusting the functioning of the maternal immune system during pregnancy. PIBF expressed by peripheral pregnancy lymphocytes, and other cell types, participates in the feto-maternal communication, partly, by mediating the immunological actions of progesterone. Several splice variants of PIBF were identified with different physiological activity. The full length 90 kD PIBF protein plays a role in cell cycle regulation, while shorter splice variants are secreted and act as cytokines. Aberrant production of PIBF isoforms lead to the loss of immune-regulatory functions, resulting in and pregnancy failure. By up regulating Th2 type cytokine production and by down-regulating NK activity, PIBF contributes to the altered attitude of the maternal immune system. Normal pregnancy is characterized by a Th2-dominant cytokine balance, which is partly due to the action of the smaller PIBF isoforms. These bind to a novel form of the IL-4 receptor, and induce increased production of IL-3, IL-4, and IL-10. The communication between the conceptus and the mother is established via extracellular vesicles (EVs). Pre-implantation embryos produce EVs both , and . PIBF transported by the EVs from the embryo to maternal lymphocytes induces increased IL-10 production by the latter, this way contributing to the Th2 dominant immune responses described during pregnancy.
妊娠是一种独特的免疫状态。尽管胚胎表达的父系抗原被母体免疫系统识别，但免疫反应并不会伤害胎儿。孕激素和孕激素诱导的蛋白（PIBF）在妊娠期间重新调整母体免疫系统的功能方面发挥着重要作用。外周妊娠淋巴细胞和其他细胞类型表达的 PIBF 参与胎-母通讯，部分通过介导孕激素的免疫作用。已经鉴定出 PIBF 的几种剪接变体，具有不同的生理活性。全长 90kD 的 PIBF 蛋白在细胞周期调节中发挥作用，而较短的剪接变体则被分泌并作为细胞因子发挥作用。PIBF 同工型的异常产生导致免疫调节功能丧失，从而导致妊娠失败。通过上调 Th2 型细胞因子的产生和下调 NK 活性，PIBF 有助于改变母体免疫系统的态度。正常妊娠的特点是 Th2 型细胞因子占优势，部分原因是较小的 PIBF 同工型的作用。这些同工型与新型 IL-4 受体结合，诱导 IL-3、IL-4 和 IL-10 的产生增加。胚胎和母体之间的通讯是通过细胞外囊泡（EVs）建立的。着床前胚胎产生 EVs，PIBF 由胚胎运输到母体淋巴细胞中，诱导后者产生更多的 IL-10，从而有助于描述妊娠期间 Th2 型免疫反应。
