title: Cyclosporine A enhances Th2 bias at the maternal-fetal interface in early human pregnancy with aid of the interaction between maternal and fetal cells.
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.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Hai-Lan
authors.initials: HL
authors.lastname: Piao
authors.forename: Song-Cun
authors.initials: SC
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.forename: Chan
authors.initials: C
authors.lastname: Sun
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Du
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000328:Adult; D002450:Cell Communication; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology*; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine