Glycodelin A induces a tolerogenic phenotype in monocyte-derived dendritic cells in vitro.
OBJECTIVE
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).


METHODS
We investigated the effect of GdA on monocyte-derived DC (moDC) regarding surface marker expression, endopinocytotic activity, cytokine profile as well as lymphoproliferative activity.


RESULTS
Upon pretreatment with GdA and subsequent maturation with tumor necrosis factor-alpha and interleukin (IL)-1beta, 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.


CONCLUSIONS
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.
Scholz
Christoph
C
Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Innenstadt, Munich, Germany. cscholz@med.lmu.de
Toth
Bettina
B
Brunnhuber
Regina
R
Rampf
Elisabeth
E
Weissenbacher
Tobias
T
Santoso
Laura
L
Friese
Klaus
K
Jeschke
Udo
U
D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins