Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde St., Toronto, ON, Canada.
J Leukoc Biol. 2012 Mar;91(3):417-26. doi: 10.1189/jlb.1011501. Epub 2012 Jan 6.
Decidualization, a progesterone-dependent process that alters endometrial stromal cells at implantation sites in humans and rodents, is accompanied by a highly regulated, NK cell-dominated leukocyte influx into decidual basalis (DB). Whether uNK cells differentiate from uterine progenitor cells is unknown, as are the mechanisms restricting leukocytes to DB. We asked if cells expressing the early NK lineage marker CD127 (IL-7Rα) occurred in mouse decidua. CD127 was absent from gd6.5 decidual lymphoid cells but became expressed by a mature uNK cell subset in gd10.5 DB. DB and transient myometrial structures (MLAp) that ring maternal blood vessels supplying placentae expressed IL-7 and TSLP, the CD127 ligands, but with differing temporal and spatial patterns. UNK cells expressed TSLPR, and study of gd10.5 implantation sites from mice deleted for IL-7, CD127, or TSLPR suggested that IL-7 and its receptor have physiological roles in limiting expansion of immature uNK cells within MLAp, while the TSLP signaling pathway is used in DB to sustain IFN-γ production from a subset of mature uNK cells. Regionalized, dynamic expression of the additional lymphoid organ stromal markers gp38/podoplanin and ER-TR7, but not CD157, were seen by immunohistochemistry in implantation sites, and DB and MLAp contained transcripts for Aire, a tolerance-promoting factor. These observations suggest that CD127(+) NK lineage progenitors are not present in the early postimplantation period of mouse uterus and that decidualized endometrial stroma has key immunoregulatory properties.
蜕膜化是一个孕激素依赖的过程，它改变了人类和啮齿动物着床部位的子宫内膜基质细胞，伴随着高度调控的、以自然杀伤（NK）细胞为主的白细胞涌入蜕膜基底（DB）。uNK 细胞是否从子宫祖细胞分化而来，以及限制白细胞进入 DB 的机制尚不清楚。我们询问了在小鼠蜕膜中是否存在表达早期 NK 谱系标记物 CD127（IL-7Rα）的细胞。CD127 在 gd6.5 蜕膜淋巴细胞中不存在，但在 gd10.5 DB 中的成熟 uNK 细胞亚群中表达。DB 和短暂的子宫肌层结构（MLAp）环绕供应胎盘的母体血管，表达 IL-7 和 TSLP，即 CD127 的配体，但具有不同的时空模式。uNK 细胞表达 TSLPR，对缺失 IL-7、CD127 或 TSLPR 的小鼠 gd10.5 着床部位的研究表明，IL-7 和其受体在限制 MLAp 内未成熟 uNK 细胞的扩张方面具有生理作用，而 TSLP 信号通路则用于 DB 中维持一部分成熟 uNK 细胞产生 IFN-γ。在着床部位的免疫组织化学研究中，观察到额外的淋巴器官基质标记物 gp38/podoplanin 和 ER-TR7 的区域性、动态表达，但 CD157 没有。DB 和 MLAp 含有促进耐受的因子 Aire 的转录本。这些观察结果表明，在小鼠子宫的早期着床期，不存在 CD127（+）NK 谱系祖细胞，并且蜕膜化的子宫内膜基质具有关键的免疫调节特性。
