Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University Magdeburg , Magdeburg , Germany ; PDBEB, Center for Neuroscience and Cell Biology, University of Coimbra , Coimbra , Portugal.
Front Immunol. 2013 Jun 20;4:158. doi: 10.3389/fimmu.2013.00158. eCollection 2013.
Implantation of the fertilized egg into the maternal uterus depends on the fine balance between inflammatory and anti-inflammatory processes. Whilst regulatory T cells (Tregs) are reportedly involved in protection of allogeneic fetuses against rejection by the maternal immune system, their role for pregnancy to establish, e.g., blastocyst implantation, is not clear. By using 2-photon imaging we show that Foxp3(+) cells accumulated in the mouse uterus during the receptive phase of the estrus cycle. Seminal fluid further fostered Treg expansion. Depletion of Tregs in two Foxp3.DTR-based models prior to pairing drastically impaired implantation and resulted in infiltration of activated T effector cells as well as in uterine inflammation and fibrosis in both allogeneic and syngeneic mating combinations. Genetic deletion of the homing receptor CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. Our results demonstrate that Tregs play a critical role in embryo implantation by preventing the development of a hostile uterine microenvironment.
受精卵植入母体子宫依赖于炎症和抗炎过程之间的精细平衡。尽管调节性 T 细胞（Tregs）据报道参与了保护同种异体胎儿免受母体免疫系统排斥，但它们在妊娠建立中的作用（例如囊胚植入）尚不清楚。通过使用双光子成像，我们发现在动情周期的接受期，Foxp3(+)细胞在小鼠子宫中积累。精液进一步促进了 Treg 的扩增。在配对前使用两种基于 Foxp3.DTR 的模型耗尽 Tregs 会严重损害植入，并导致激活的 T 效应细胞浸润以及同种异体和同基因交配组合中的子宫炎症和纤维化。归巢受体 CCR7 的基因缺失干扰了 Tregs 在子宫中的积累和植入，表明 Tregs 向子宫的归巢是由 CCR7 介导的。我们的研究结果表明，Tregs 通过防止子宫微环境变得敌对，在胚胎植入中发挥关键作用。
