Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice
Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice
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DOI：
10.1172/jci38714
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发表时间：
2009-07-01
影响因子：
15.9
通讯作者：
Erlebacher, Adrian
中科院分区：
文献类型：
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作者：
Collins, Mary K.;Tay, Chin-Siean;Erlebacher, Adrian
胚胎着床诱导蜕膜的形成，蜕膜是一种间质细胞衍生的结构，包裹着胎儿和胎盘。用小鼠作为模型生物，我们发现这种组织反应阻止了位于母胎界面的dc迁移到子宫淋巴管，从而到达引流淋巴结。引人注目的是，即使在LPS刺激下，个体DC仍保持不动，并表现出对CCL21的反应，CCL21是驱动DC进入淋巴管的趋化因子。母体T细胞对代胎/胎盘抗原的反应性分析进一步表明，局部T细胞对胎儿和胎盘的反应是由被动抗原运输驱动的，因此，当组织内dc的输入微不足道时，抗原呈递的耐受性模式占主导地位。事实上，组织驻留dc在T细胞对胎儿同种异体移植物的反应中缺乏参与，这与它们在器官移植排斥中的突出作用形成鲜明对比。我们的研究结果表明，DC包埋在蜕膜内减少了免疫原性T细胞对胎儿/胎盘抗原的暴露，并提高了人类蜕膜发育或功能受损的可能性，与小鼠不同，蜕膜含有淋巴管，可能导致怀孕期间病理性T细胞活化。
Embryo implantation induces formation of the decidua, a stromal cell-derived structure that encases the fetus and placenta. Using the mouse as a model organism, we have found that this tissue reaction prevents DCs stationed at the maternal/fetal interface from migrating to the lymphatic vessels of the uterus and thus reaching the draining lymph nodes. Strikingly, decidual DCs remained immobile even after being stimulated with LPS and exhibiting responsiveness to CCL21, the chemokine that drives DC entry into lymphatic vessels. An analysis of maternal T cell reactivity toward a surrogate fetal/placental antigen furthermore revealed that regional T cell responses toward the fetus and placenta were driven by passive antigen transport and thus the tolerogenic mode of antigen presentation that predominates when there is negligible input from tissue-resident DCs. Indeed, the lack of involvement of tissue-resident DCs in the T cell response to the fetal allograft starkly contrasts with their prominent role in organ transplant rejection. Our results suggest that DC entrapment within the decidua minimizes immunogenic T cell exposure to fetal/placental antigens and raise the possibility that impaired development or function of the human decidua, which unlike that of the mouse contains lymphatic vessels, might lead to pathological T cell activation during pregnancy.