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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 7

Decidualization reduces DC migration from the uterus to the draining LNs.

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Decidualization reduces DC migration from the uterus to the draining LNs...
Mice with artificially decidualized or undecidualized uteri were injected transcervically with CFSE and sacrificed 28 hours later. (A and B) Transverse sections of uteri from uninjected (A) or CFSE-injected (B) mice were stained for CFSE using anti-FITC antibodies and counterstained with DAPI. Insets show undecidualized uteri magnified to the same extent as decidualized uteri. The myometrium has partially peeled away from the decidua in A. All images were subjected to same nonlinear adjustment so that CFSE staining intensities would be comparable, yet visible in a panoramic view. Scale bar: 1 mm (applies to all images). (C) Gating scheme and representative histograms showing the appearance of CFSE+ migratory DCs in the uterine LNs. Cells were gated on B220– cells to exclude B cells and thus help clarify the MHCIIhiCD11cint migratory DC population (see Figure 1E). Shaded and open histograms are from untreated and CFSE-injected mice, respectively. The percentage of CFSE+ cells was determined by setting the lower bound of the marker to give approximately 1% positive cells in the non-CFSE-injected group. (D) Mean percentage of CFSE+ migratory DCs (± SEM; n = 6 mice per group).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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