Effect of Cyclosporine A on Th1/Th2 Cytokine Production by Decidual Stromal Cells Mediated by Trophoblast-derived Galectin-9

This study aimed to investigate the effect of cyclosporine A (CsA) on secretion of Th1 and Th2 cytokines by decidual stromal cells (DSCs) mediated by galectin (Gal)-9.HTR8/SVneo cells and primary trophoblasts were used for in vitro studies. Gal-9 expression was measured using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, CsA was used to regulate Gal-9 expression in trophoblasts. DSCs were treated with trophoblast supernatant and changes in Th1 and Th2 cytokine levels were analyzed. Changes in DSC levels of the T-cell immunoglobulin mucin receptor 3 (TIM-3) levels in DSCs after treatment with Gal-9 were assessed. Western blotting and ERK and AKT inhibitors were used to assess the involvement of the corresponding signaling pathways. Gal-9 was expressed by both primary trophoblasts and HTR8/SVneo cells. CsA treatment increased Gal-9 secretion by trophoblasts, which in turn increased IL-6 (Th2 cytokine) and decreased TNF-alpha and IFN-gamma (Th1 cytokines) secretion in DSCs. Upon downregulation of trophoblast Gal-9 secretion, DSCs secreted lower levels of Th2 cytokines and higher levels of Th1 cytokines, and the effect was reversed by addition of CsA. TIM-3 expression changed in parallel with Gal-9 secretion. CsA treatment upregulated expression of Gal-9 in trophoblasts, promoted secretion of Th2 cytokines, and inhibited secretion of Th1 cytokines via ERK signaling.