| 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 show that this process prevents dendritic cells (DCs) stationed at the maternal/fetal interface from migrating to the lymphatic vessels of the uterus. As a result, the cells cannot reach the draining lymph nodes to participate in regional T cell responses towards fetal/placental antigens. These responses are instead promoted by the inherently more tolerogenic route of passive antigen transport. Strikingly, decidual DCs remain immobile even following their LPS-induced maturation and upregulation of CCR7, the chemokine receptor that drives DC entry into lymphatic vessels. Additional evidence suggests that DC entrapment may be attributable to changes in the ECM composition that occur during decidualization, or changes in the expression pattern of a chemoattractant that signals independently of CCR7. Interestingly, decidual DCs do not appear to markedly drive T cell proliferation within the implantation site either. This result bolsters the newly developing hypothesis that their role in the maternal/fetal interface is not as an antigen-presenting cell, but instead to promote decidualization, placenta formation and angiogenesis. The lack of involvement of tissue-resident DCs in the T cell response to the fetal allograft starkly contrasts with the central role of these cells as instigators of organ transplant rejection. Establishing fetomaternal tolerance through the generation of a unique, pregnancy-specific anatomical structure prohibitive for DC migration raises the possibility that impaired development or function of the human decidua, which unlike the mouse contains lymphatic vessels, might lead to pathological T cell activation during pregnancy. |
