Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat.
Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat.
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DOI：
10.1186/1743-422x-9-88
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发表时间：
2012-05-04
期刊：
影响因子：
4.8
通讯作者：
Coats KS
中科院分区：
文献类型：
--
作者：
Boudreaux CE;Chumbley LB;Scott VL;Wise DA;Coats KS
胎盘调节性T细胞(Tregs)(免疫抑制细胞群)和Th17细胞(促炎症细胞群)的适当平衡对于半异基因胎儿的耐受至关重要。转化生长因子-β和IL-6是促进Tregs和Th17细胞从共同的祖细胞分化而来的细胞因子；细胞因子的异常表达可能会扰乱这两个细胞群体的平衡。我们先前报告了胎盘的促炎环境，在怀孕早期感染FIV的猫的胎盘中，Treg标志物FoxP3的水平降低，IL-6的水平上升。因此，我们假设怀孕的猫感染FIV会引起胎盘Treg和Th17细胞群的改变，可能导致胎盘炎症。我们通过定量共聚焦显微镜检测Th17标志物FoxP3或RoRγ，以及定量聚合酶链式反应(QPCR)定量检测关键细胞因子转化生长因子β和IL-6的表达，研究了FIV感染对妊娠早期胎盘中Treg和Th17群体的影响。Foxp3和RoRγ在妊娠早期感染的胎盘中呈正相关，而在正常猫胎盘中不相关，表明病毒诱导的这些细胞群的平衡发生了变化。在对照猫中，IL-6和RoRγ的表达如预期的那样呈正相关，但在感染动物中这种关系被破坏。转化生长因子-β在受感染的蜂王体内减少，这种情况可能会扰乱Treg和Th17细胞的数量。共表达分析显示，IL-6和转化生长因子-β在对照动物中的表达呈高度显著的正相关，而在感染动物中则不存在。总体而言，这些数据表明Treg和Th17细胞群平衡的潜在破坏可能导致FIV诱导的猫胎盘炎症。
An appropriate balance in placental regulatory T cells (Tregs), an immunosuppressive cell population, and Th17 cells, a pro-inflammatory cell population, is essential in allowing tolerance of the semi-allogeneic fetus. TGF-β and IL-6 are cytokines that promote differentiation of Tregs and Th17 cells from a common progenitor; aberrant expression of the cytokines may perturb the balance in the two cell populations. We previously reported a pro-inflammatory placental environment with decreased levels of FoxP3, a Treg marker, and increased levels of IL-6 in the placentas of FIV-infected cats at early pregnancy. Thus, we hypothesized that FIV infection in the pregnant cat causes altered placental Treg and Th17 cell populations, possibly resulting in placental inflammation. We examined the effect of FIV infection on Treg and Th17 populations in placentas at early pregnancy using quantitative confocal microscopy to measure FoxP3 or RORγ, a Th17 marker, and qPCR to quantify expression of the key cytokines TGF-β and IL-6. FoxP3 and RORγ were positively correlated in FIV-infected placentas at early pregnancy, but not placentas from normal cats, indicating virus-induced alteration in the balance of these cell populations. In control cats the expression of IL-6 and RORγ was positively correlated as predicted, but this relationship was disrupted in infected animals. TGF-β was reduced in infected queens, an occurrence that could dysregulate both Treg and Th17 cell populations. Co-expression analyses revealed a highly significant positive correlation between IL-6 and TGF-β expression in control animals that did not occur in infected animals. Collectively, these data point toward potential disruption in the balance of Treg and Th17 cell populations that may contribute to FIV-induced inflammation in the feline placenta.