Myeloid and plasmacytoid dendritic cell subsets are differentially regulated by the pregnancy hormone human Chorionic Gonadotropin

Abstract

Abstract Dendritic cells (DCs) are critically involved in the establishment and maintenance of fetal tolerance. However, the precise mechanisms underlying their regulation during pregnancy are still not defined. The placenta-derived hormone human Chorionic Gonadotropin (hCG) possesses immune modulatory properties and is commonly used in artificial reproductive techniques (ART). Here, we analyzed the effect of placenta-derived hCG and two hCG preparations on different DC subsets. After isolation from peripheral blood of non pregnant women, DCs were stimulated with LPS to induce maturation. In parallel, DCs were co-cultured with placenta-derived hCG (JEG-3 cells), with urine-derived hCG or recombinant hCG. The total number and maturation state of two myeloid DC (MDC1; MDC2) and one plasmacytoid DC subset (PDC) was evaluated. Additionally, the levels of IL-6, IL-8, IL-10, IL-12 and TNF were determined in co-culture supernatants. In all experiments, unstimulated DCs and stimulated DCs cultured alone served as controls. JEG-3 impaired the LPS-induced increase of total MDC1 while both hCG preparations hindered the increment of total MDC1 and MDC2. Moreover, JEG-3 interfered with PDC and MDC1 maturation while both hCG preparations hampered maturation of all DC subsets. However, significant effects could only be observed on the MDC1 subset. Cytokine assays revealed that JEG-3 and both hCG preparations impaired LPS-induced secretion of all analyzed cytokines. Our results suggest that hCG from distinct sources regulates DC subsets in a different manner. This information does not only contribute to our understanding of a differential regulation of various DC subsets during pregnancy but is also relevant for the use of hCG preparations in ART.