Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Science. 2012 Jun 8;336(6086):1317-21. doi: 10.1126/science.1220030.
The chemokine-mediated recruitment of effector T cells to sites of inflammation is a central feature of the immune response. The extent to which chemokine expression levels are limited by the intrinsic developmental characteristics of a tissue has remained unexplored. We show in mice that effector T cells cannot accumulate within the decidua, the specialized stromal tissue encapsulating the fetus and placenta. Impaired accumulation was in part attributable to the epigenetic silencing of key T cell-attracting inflammatory chemokine genes in decidual stromal cells, as evidenced by promoter accrual of repressive histone marks. These findings give insight into mechanisms of fetomaternal immune tolerance, as well as reveal the epigenetic modification of tissue stromal cells as a modality for limiting effector T cell trafficking.
趋化因子介导的效应 T 细胞向炎症部位的募集是免疫反应的一个核心特征。趋化因子表达水平在多大程度上受到组织固有发育特征的限制，这一点仍未得到探索。我们在小鼠中表明，效应 T 细胞不能在蜕膜（包裹胎儿和胎盘的特化基质组织）内积聚。这种积累的受损部分归因于蜕膜基质细胞中关键吸引 T 细胞的炎症趋化因子基因的表观遗传沉默，这可以通过促进抑制性组蛋白标记物的募集来证明。这些发现深入了解了胎母免疫耐受的机制，并揭示了组织基质细胞的表观遗传修饰作为限制效应 T 细胞迁移的一种方式。
