Abstract
Our previous study has demonstrated that cyclosporine A (CsA) administration in vivo induces Th2 bias at the maternal-fetal interface, leading to improved murine pregnancy outcomes. Here, we investigated how CsA treatment in vitro induced Th2 bias at the human maternal-fetal interface in early pregnancy. The cell co-culture in vitro in different combination of component cells at the maternal-fetal interface was established to investigate the regulation of CsA on cytokine production from the interaction of these cells. It was found that interferon (IFN)-γ was produced only by decidual immune cells (DICs), and not by trophoblasts or decidual stromal cells (DSCs); all these cells secreted interleukin (IL)-4, IL-10, and tumor necrosis factor (TNF)-α. Treatment with CsA completely blocked IFN-γ production in DICs and inhibited TNF-α production in all examined cells. CsA increased IL-10 and IL-4 production in trophoblasts co-cultured with DSCs and DICs although CsA treatment did not affect IL-10 or IL-4 production in any of the cells when cultured alone. These results suggest that CsA promotes Th2 bias at the maternal-fetal interface by increasing Th2-type cytokine production in trophoblasts with the aid of DSCs and DICs, while inhibiting Th1-type cytokine production in DICs and TNF-α production in all investigated cells. Our study might be useful in clinical therapeutics for spontaneous pregnancy wastage and other pregnancy complications.
Highlights
Successful pregnancy requires delicate harmony between fetusderived trophoblast cells and mother-derived decidual cells
decidual stromal cells (DSCs) or decidual immune cells (DICs) were cultured in 24-well plates for 24–72 h, and the release of soluble cytokines into the culture supernatant was detected by using enzymelinked immunosorbent assay (ELISA) at 24-h intervals
No IFN-c secretion was seen in primary DSCs, and the secretion of IL-4, IL-10, and tumor necrosis factor (TNF)-a was 183.63621.81, 84.55618.66, 120.93643.42, respectively by DSCs after 72h of culture
Summary
Successful pregnancy requires delicate harmony between fetusderived trophoblast cells and mother-derived decidual cells. These cells synchronize to establish a unique maternal-fetal immune milieu via the production of regulatory factors, which contribute to fetal survival and development in the maternal uterus until parturition [1,2,3]. Cytokines appear to play an important role in modulating and integrating immune and endocrine systems for the maintenance of maternal-fetal tolerance and sufficient placentation. The maintenance of the Th2-predominant environment both at the maternal-fetal interface and in the periphery is considered an important target in the treatment of unexplained pregnancy loss
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