ORIGINAL ARTICLE: Impact of Female Sex Hormones on the Maturation and Function of Human Dendritic Cells

Authors


Sabine E. Segerer, Department of Obstetrics and Gynaecology, University of Würzburg, Josef-Schneider Str. 4, D-97080 Würzburg, Germany.
E-mail: engert_s1@klinik.uni-wuerzburg.de

Abstract

Problem  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.

Methods/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.

Conclusion  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.

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