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Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice
Mary K. Collins, … , Chin-Siean Tay, Adrian Erlebacher
Mary K. Collins, … , Chin-Siean Tay, Adrian Erlebacher
Published June 22, 2009
Citation Information: J Clin Invest. 2009;119(7):2062-2073. https://doi.org/10.1172/JCI38714.
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Research Article Article has an altmetric score of 1

Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice

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Abstract

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.

Authors

Mary K. Collins, Chin-Siean Tay, Adrian Erlebacher

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Figure 9

Decidual DCs retain their cell-intrinsic maturation and migratory capacity yet are trapped within the tissue.

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Decidual DCs retain their cell-intrinsic maturation and migratory capaci...
(A) CD86 and CCR7 expression levels on MHCII+F4/80–CD11chi uterine DCs. The cells were harvested on E7.5 from untreated mice or mice that had been intravenously injected 15 hours earlier with 30 ng LPS. Percentages of cells with the indicated levels of expression are shown. Data are representative of n = 3 mice per group. (B) Ex vivo migration of cells from the myometrium or decidua toward medium alone or medium containing CCL21. The Transwell migration of DCs (MHCII+F4/80–CD11chi) and MHCII+ macrophages (MHCII+F4/80+) from MHCII+ MACS-purified cells (left panel) or total disaggregated cells (right panel) are expressed as a percentage of their respective input cell number. The cells were isolated on E7.5 fifteen hours after the intravenous injection of 30 ng LPS. Data are mean ± SEM of 2 wells per group. These experiments were replicated 3 times with similar results. The middle panel shows the total number of cells (mean ± SEM of 5 mice per group compiled over 3 independent experiments) that emigrated out of intact tissue explants.

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