Cyclosporine A enhances Th2 bias at the maternal-fetal interface in early human pregnancy with aid of the interaction between maternal and fetal cells

• Published in: PloS one 2012-09, Vol.7 (9), p.e45275-e45275
• Main Authors: Piao, Hai-Lan, Wang, Song-Cun, Tao, Yu, Zhu, Rui, Sun, Chan, Fu, Qiang, Du, Mei-Rong, Li, Da-Jin
• Format: Article
• Language: English
• Subjects: Abortion; Adult; Bias; Biology; Cell Communication; Cell culture; Coculture Techniques; Complications; Complications and side effects; Cyclosporine - pharmacology; Cyclosporins; Cytokines; Decidua; Decidua - cytology; Decidua - drug effects; Decidua - metabolism; Dosage and administration; Female; Fetuses; Genetic aspects; Gynecology; Humans; Immune system; Immunology; Immunosuppressive Agents - pharmacology; In vivo methods and tests; Interferon; Interferon-gamma - biosynthesis; Interleukin; Interleukin 10; Interleukin 4; Interleukin-10 - biosynthesis; Interleukin-4 - biosynthesis; Kinases; Laboratories; Lymphocytes T; Medicine; Obstetrics; Physiological aspects; Pregnancy; Pregnancy complications; Pregnancy Trimester, First; Rheumatoid arthritis; Risk factors; Signal transduction; Stromal cells; Th1 Cells - cytology; Th1 Cells - drug effects; Th1 Cells - metabolism; Th1-Th2 Balance; Th2 Cells - cytology; Th2 Cells - drug effects; Th2 Cells - metabolism; Trophoblasts; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045275

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.