Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy.
Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy.
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DOI：
10.1084/jem.192.2.259
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发表时间：
2000-07-17
影响因子：
15.3
通讯作者：
Croy, B A
中科院分区：
文献类型：
--
作者：
Ashkar, A A;Di Santo, J P;Croy, B A
人类和小鼠着床部位的主要淋巴细胞是短暂的、与妊娠相关的子宫自然杀伤细胞（uNK）。这些细胞是干扰素(IFN)-γ的主要来源。在缺乏nk细胞（淋巴重组酶激活基因[RAG]-2−/−共同细胞因子受体链γ [γc]−/−）或IFN-γ信号（IFN-γ−/−或IFN-γ - r α−/−）的小鼠中，植入部位不能启动正常的妊娠诱导的蜕膜动脉修饰，并表现为蜕膜细胞增多或坏死。为了研究uNK细胞衍生的IFN-γ在怀孕期间的功能，rag2 - / -γ - c - / -雌性小鼠被植入IFN-γ - / -小鼠、IFN-γ信号中断小鼠（IFN-γ r - / -或信号转换器和转录激活因子[Stat]-1 - / -）或能够建立正常uNK细胞的小鼠（严重联合免疫缺陷[SCID]或C57BL/6）的骨髓。配对受体在妊娠中期进行分析。所有移植物均建立了uNK细胞。来自IFN-γ−/−小鼠的移植物没有逆转宿主血管或蜕膜病理。所有其他供体的移植物都促进了蜕膜动脉和蜕膜细胞的改变。IFN-γ - r α−/−或Stat-1−/−小鼠的移植物过量产生未成熟的uNK细胞。IFN-γ−/−、SCID或C57BL/6小鼠的移植物产生正常、成熟的uNK细胞。在没有uNK细胞的情况下，给怀孕的rag2 - / -γ - c - / -小鼠注射小鼠重组IFN-γ，启动了蜕膜血管修饰，促进了蜕膜细胞的分化。这些体内研究结果强烈表明，uNK细胞来源的IFN-γ改变了子宫血管和基质中基因的表达，从而引发血管不稳定，促进妊娠诱导的蜕膜动脉重塑。
The dominant lymphocytes in human and murine implantation sites are transient, pregnancy-associated uterine natural killer (uNK) cells. These cells are a major source of interferon (IFN)-γ. Implantation sites in mice lacking uNK cells (alymphoid recombinase activating gene [RAG]-2−/− common cytokine receptor chain γ [γc]−/−) or IFN-γ signaling (IFN-γ−/− or IFN-γRα−/−) fail to initiate normal pregnancy-induced modification of decidual arteries and display hypocellularity or necrosis of decidua. To investigate the functions of uNK cell–derived IFN-γ during pregnancy, RAG-2−/−γc −/− females were engrafted with bone marrow from IFN-γ−/− mice, IFN-γ signal-disrupted mice (IFN-γRα−/− or signal transducer and activator of transcription [Stat]-1−/−), or from mice able to establish normal uNK cells (severe combined immunodeficient [SCID] or C57BL/6). Mated recipients were analyzed at midgestation. All grafts established uNK cells. Grafts from IFN-γ−/− mice did not reverse host vascular or decidual pathology. Grafts from all other donors promoted modification of decidual arteries and decidual cellularity. Grafts from IFN-γRα−/− or Stat-1−/− mice overproduced uNK cells, all of which were immature. Grafts from IFN-γ−/−, SCID, or C57BL/6 mice produced normal, mature uNK cells. Administration of murine recombinant IFN-γ to pregnant RAG-2−/−γc −/− mice initiated decidual vessel modification and promoted decidual cellularity in the absence of uNK cells. These in vivo findings strongly suggest that uNK cell–derived IFN-γ modifies the expression of genes in the uterine vasculature and stroma, which initiates vessel instability and facilitates pregnancy-induced remodeling of decidual arteries.