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

MK Collins, CS Tay, A Erlebacher - The Journal of clinical …, 2009 - Am Soc Clin Investig
MK Collins, CS Tay, A Erlebacher
The Journal of clinical investigation, 2009Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation