Impact of female sex hormones on the maturation and function of human dendritic cells.
OBJECTIVE
During pregnancy, the immune and the endocrine system cooperate to ensure that the fetal allograft develops without eliciting a maternal immune response. This is presumably in part achieved by dendritic cells (DCs) that play a dominant role in maintaining peripheral tolerance. In this study, we investigated whether female sex hormones, such as human chorionic gonadotropin (hCG), progesterone (Prog), and estradiol (E2), which are highly elevated during pregnancy, induce the differentiation of DCs into a tolerance-inducing phenotype.


RESULTS
Immature DCs were generated from blood-derived monocytes and differentiated in the presence of hCG, Prog, E2, or Dexamethasone (Dex) as a control. Unlike Dex, female sex hormones did not prevent the upregulation of surface markers characteristic for mature DCs, such as CD40, CD83, and CD86, except for hCG, which inhibited HLA-DR expression. Similarly, hCG, Prog, and E2 had any impact on neither the rearrangement of the F-actin cytoskeleton nor the enhanced chemokine secretion following DC maturation, both of which were strongly altered by Dex. Nevertheless, the T-cell stimulatory capacity of DCs was significantly reduced after hCG and E2 exposure.


CONCLUSIONS
Our findings suggest that the female sex hormones hCG and E2 inhibit the T-cell stimulatory capacity of DCs, which may help in preventing an allogenic T-cell response against the embryo.
Segerer
Sabine E
SE
Department of Obstetrics and Gynaecology, University of Würzburg, Würzburg, Germany. engert_s1@klinik.uni-wuerzburg.de
Müller
Nora
N
van den Brandt
Jens
J
Kapp
Michaela
M
Dietl
Johannes
J
Reichardt
Holger M
HM
Rieger
Lorenz
L
Kämmerer
Ulrike
U
D000199:Actins / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D011374:Progesterone / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects
D000199:Actins; D015415:Biomarkers; D006063:Chorionic Gonadotropin; D016207:Cytokines; D011374:Progesterone; D004958:Estradiol