Table_1_Decidualized human decidual stromal cells inhibit chemotaxis of activated T cells: a potential mechanism of maternal-fetal immune tolerance.docx

BackgroundNumerous lines of evidence confirm that decidual stromal cells (DSCs) play a key role in maternal–fetal immune tolerance. Under the influence of progesterone and other hormones, the DSCs go through a process of differentiation (decidualization) during normal pregnancy. In mice, DSCs inhibit the expression of chemokines that attract abortigenic Th1 and Tc cells to the decidua. We have studied this phenomenon in humans.
MethodsWe established human DSC lines and decidualized these cells in vitro with progesterone and cAMP. We determined the expression of the chemokines CXCL9, CXCL10 and CXCL11, whose receptor CXCR3 is expressed by Th1 and Tc cells, in undifferentiated DSCs and decidualized DSCs by qRT-PCR. Activated CD3+CXCR3+ cells, including CD4+ Th1 cells and CD8+ Tc cells, were induced in vitro. The migration capacity of these activated lymphocytes was investigated in Transwell chambers with conditioned media from undifferentiated and decidualized DSCs.
ResultsWe demonstrated that CXCL9 was not expressed by DSCs, whereas the expression of CXCL10 and CXCL11 was inhibited in decidualized cells. Conditioned media from decidualized cells significantly inhibited the migration of Th1 and Tc cells. We found that decidualized cells secrete factors of MW less than 6000–8000 Da, which actively inhibit the chemotaxis of these lymphocytes.
DiscussionThese results confirm in humans that decidualization of DSCs inhibits the expression by these cells of chemokines that attract Th1 and Tc cells and induces the secretion by DSCs of factors that inhibit the chemotaxis of these lymphocytes, thus preventing the arrival of abortigenic T cells in the decidua.

背景 大量研究证据证实，蜕膜基质细胞（decidual stromal cells, DSCs）在母胎免疫耐受中发挥关键作用。在孕酮及其他激素的调控下，正常妊娠过程中蜕膜基质细胞会经历分化（蜕膜化）过程。在小鼠模型中，蜕膜基质细胞可抑制趋化因子的表达，这类趋化因子会将致流产性Th1细胞与Tc细胞招募至蜕膜组织。本研究针对人类中的该现象展开了探究。
方法 本研究构建了人源蜕膜基质细胞系，并通过孕酮与环磷酸腺苷（cAMP）在体外对这些细胞进行蜕膜化诱导。本研究采用实时荧光定量PCR（qRT-PCR），检测未分化蜕膜基质细胞与蜕膜化蜕膜基质细胞中CXCL9、CXCL10及CXCL11的表达水平；上述趋化因子的受体CXCR3可在Th1细胞与Tc细胞表面表达。本研究体外诱导获得活化的CD3+CXCR3+细胞，其中包含CD4+ Th1细胞与CD8+ Tc细胞。本研究采用铺有未分化与蜕膜化蜕膜基质细胞条件培养基的Transwell小室，探究上述活化淋巴细胞的迁移能力。
结果 本研究证实，蜕膜基质细胞不表达CXCL9，而蜕膜化细胞中CXCL10与CXCL11的表达受到显著抑制。蜕膜化细胞的条件培养基可有效抑制Th1细胞与Tc细胞的迁移能力。本研究发现，蜕膜化细胞可分泌分子量介于6000~8000道尔顿（Da）以下的活性因子，该类因子可主动抑制上述淋巴细胞的趋化作用。
讨论 本研究结果在人类样本中证实，蜕膜基质细胞的蜕膜化过程可抑制自身表达招募Th1与Tc细胞的趋化因子，并诱导自身分泌抑制上述淋巴细胞趋化的活性因子，从而阻止致流产性T细胞浸润至蜕膜组织。