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

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.

Immunological role of vitamin D at the maternal–fetal interface

“…In murine models of pregnancy, a phenomenon known as 'DC entrapment' has been reported, where decidual DCs fail to migrate to uterine lymph nodes following their activation (Collins et al 2009). It has been postulated that this may serve to limit adaptive T cell responsiveness towards fetal/placental antigens and restrict immunosurveillance specifically at the maternal-fetal interface.…”

Natural killer cell-triggered vascular transformation: maternal care before birth?

“…Pregnancy induces changes in lymphoid organs, inducing, for example, thymic depletion 53,54 and blockade of dendritic cell movement to uterine-draining lymph nodes. 55 Several investigators suggest that in women, as in mice, uNK cell progenitors are of mixed endometrial and peripheral origins.…”

MicroRNAs, immune cells and pregnancy

“…Extensive literature documents the presence of immune cells at the maternal-fetal interface. [13][14][15][16][17][18][19] However, it is not entirely clear how these immune cells are recruited or their pregnancy specific functions. Studies over the past few decades have suggested the presence of progenitor stem cells in the uterus that differentiate during early pregnancy 20 and/or that immune cells are recruited from the peripheral blood by conceptus-dependent or -independent signals.…”