PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF-β1 Pathway.
PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF-β1 Pathway.
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DOI：
10.1371/journal.pone.0158050
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Dveksler G
中科院分区：
文献类型：
--
作者：
Jones K;Ballesteros A;Mentink-Kane M;Warren J;Rattila S;Malech H;Kang E;Dveksler G
妊娠特异性糖蛋白(PSGs)是由胎盘合体滋养层细胞分泌的一类蛋白质，是妊娠晚期母体血液中含量最丰富的滋养层蛋白质。人类PSG家族由10个蛋白质编码基因组成，其中一些基因可能在维持母体对胎儿的免疫耐受方面发挥作用。PSG9被报道为先兆子痫的潜在预测生物标志物，先兆子痫是妊娠的一种严重并发症，与胎儿-母体界面的免疫功能障碍有关。因此，我们推测PSG9在妊娠期间可能具有免疫调节作用。我们发现PSG_9能与LAP结合并激活潜伏型转化生长因子-β_1。此外，PSG_9能诱导巨噬细胞分泌转化生长因子-β_1，但不能诱导CD_4~+T细胞分泌转化生长因子-CD4_1。转化生长因子-β-1是调节性T细胞体外分化所必需的，与PSG9激活这一细胞因子的能力一致，我们观察到PSG9诱导幼稚小鼠和人T细胞分化为FoxP3+调节性T细胞。与炎症反应相关的细胞因子也在经PSG9处理后的T细胞上清液中减少，提示PSG9通过激活转化生长因子β-1可能是一种有效的免疫耐受诱导剂。
The pregnancy-specific glycoproteins (PSGs) are a family of proteins secreted by the syncytiotrophoblast of the placenta and are the most abundant trophoblastic proteins in maternal blood during the third trimester. The human PSG family consists of 10 protein-coding genes, some of which have a possible role in maintaining maternal immune tolerance to the fetus. PSG9 was reported as a potential predictive biomarker of pre-eclampsia, a serious complication of pregnancy that has been related to immunological dysfunction at the fetal-maternal interface. Therefore, we hypothesized that PSG9 may have an immunoregulatory role during pregnancy. We found that PSG9 binds to LAP and activates the latent form of TGF-β1. In addition, PSG9 induces the secretion of TGF-β1 from macrophages but not from CD4+ T-cells. TGF-β1 is required for the ex vivo differentiation of regulatory T-cells and, consistent with the ability of PSG9 to activate this cytokine, we observed that PSG9 induces the differentiation of FoxP3+ regulatory T-cells from naïve murine and human T-cells. Cytokines that are associated with inflammatory responses were also reduced in the supernatants of T-cells treated with PSG9, suggesting that PSG9, through its activation of TGFβ-1, could be a potent inducer of immune tolerance.