Placental trophoblasts shifted Th1/Th2 balance toward Th2 and inhibited Th17 immunity at fetomaternal interface

Abstract

The aims were to clarify the effect of placental trophoblasts on T lymphocytes by assessing production of cytokines and expression of transcription factors regulating Th1, Th2, and Th17 immunity in T lymphocytes. Placental trophoblasts were isolated and conditioned medium was made after trophoblast cultivation for 72 h. T lymphocytes were cultured in presence or absence of conditioned medium. ELISA was used to detect concentration of IL-2, TNF-α, IFN-γ, IL-4, IL-10, and IL-17 in supernatants of T cell and real-time PCR was used to detect the status of Th1 (T-bet, STAT-4), Th2 (GATA-3, STAT-6), and Th17 (RORC) immunity in T lymphocyte. We found that the level of IL-2, IFN-γ, TNF-α, and IL-17 was significantly decreased when T lymphocytes were cultured in conditioned medium compared with control, while IL-10 and IL-4 level were not significantly changed. The presence of conditioned medium significantly decreased the ratio of Th1/Th2. The expression of GATA-3 and STAT-6 were significantly increased and STAT-4 was reduced when T lymphocyte was cultured in conditioned medium, while the expression of T-bet and RORC was not significantly different. We concluded that placental trophoblast-induced shift of Th1/Th2 balance toward Th2 and inhibition of Th17 might be among the mechanisms involved in maternal tolerance to fetus.

The CXCL12/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal/fetal interface in early human pregnancy

“…22,25 The explanation for this discrepancy might be that others treated peripheral T cells rather than decidual T cells with trophoblast-cultured supernatant, rather than direct coculture with the trophoblast. Our unpublished data show similar effects of trophoblasts and DSCs on peripheral immune cells.…”

“…Placental trophoblasts decrease the production of Th1-type and Th17-type cytokines by peripheral T lymphocytes, inhibit the expression of transcription factors required for Th1 immunity and enhance the expression of transcription factors required for Th2 immunity. 22 Our previous study has demonstrated that trophoblasts can confer to decidual dendritic cells the ability to induce differentiation of Th0 into Th2 cells via the secretion of thymic stromal lymphopoietin in early human pregnancy. 23 Recently, we have confirmed that the first-trimester human trophoblast cells secrete chemokine (C-X-C motif) ligand 12 (CXCL12) which, in addition to inducing trophoblast proliferation and mediating crosstalk between trophoblasts and DSCs, can also recruit CD56 bright CD16 2 natural killer cells into the decidua by its interaction with chemokine (C-X-C motif) receptor 4 (CXCR4).…”

THE ROLE OF THE DIFFERENT SUBPOPULATIONS OF CD4⁺Т LYMPHOCYTES DURING PREGNANCY

“…It has been found that trophoblast secretory products reduce expression of STAT4 (specific for Th1 cells) transcription factors in T cells and stimulate expression of GATA3 and STAT6 (specific for Th2 cells) [63]. Secretory products of placenta, isolated cells of cytotrophoblast and syncytiotrophoblast stimulate CD4 [120].…”

Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus

“…[73] Wang et al have shown that Th17 cells increase in patients with recurrent spontaneous abortion that is accompanied by the decrease of Tregs. They also reported a disruption in regulation of Th17 cells by Tregs in these patients.…”