Glycodelin A Induces a Tolerogenic Phenotype in Monocyte-Derived Dendritic Cells In vitro

Successful mammalian pregnancy requires a delicate immunological balance at the feto-maternal interface that allows the semi-allogeneic fetus to grow, while protecting mother and child from environmental pathogens. As in other mucosal tissues, antigen-recognition and -handling by professional antigen-presenting cells such as dendritic cells (DC) determine the course of the subsequent immune response. DC at the feto-maternal interface help shape this immunological equilibrium. Endometrial tissue secretes high quantities of glycodelin A (GdA) during the so-called fertile window (i.e. the time of implantation of the blastocyst). We investigated the effect of GdA on monocyte-derived DC (moDC) regarding surface marker expression, endopinocytotic activity, cytokine profile as well as lymphoproliferative activity. Upon pretreatment with GdA and subsequent maturation with tumor necrosis factor-alpha and interleukin (IL)-1 beta, moDC displayed a reduced expression of costimulatory molecules, an unchanged major histocompatibility complex-II expression and persistence of DC-SIGN positive cells. GdA-pretreated moDC had a higher endopinocytotic activity, an increased IL-10 production and a dose-dependent reduction in lymphoproliferative activity. GdA incubation alone did not alter the immature phenotype. Our results suggest a model in which the human endometrium secretes high quantities of GdA during implantation and thereby helps to shape the unique immunological interaction between mother and fetus via decidual DC.