The Balance between Conventional DCs and Plasmacytoid DCs Is Pivotal for Immunological Tolerance during Pregnancy in the Mouse.

Dendritic cells (DCs), which can shape their functions depending on the microenvironment, are crucial for the delicate balance of immunity and tolerance during pregnancy. However, the mechanism underlying the microenvironment-educated plasticity of DC differentiation during pregnancy remains largely unclear. Here, we found that the differentiation of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) is regulated in a tissue-specific manner during pregnancy. The ratio of cDCs and pDCs remained constant in the spleen. However, the ratio changed in the para-aortic lymph nodes (LNs), where cDC percentages were significantly reduced concurrent with an increase in pDCs from E8.5 to E16.5. Moreover, the expansion of pDCs and T regulatory (Treg) cells was correlated in the para-aortic LNs, and pDCs had more potential to induce regulatory T cells (Tregs) compared with cDCs (independent of IDO expression). Notably, the balance between cDCs and pDCs is disrupted in IFN-γ-induced abnormal pregnancy, accompanied by lower Treg percentages in the para-aortic LNs and decidua. To further identify the underlying mechanism, we found that elevated IFN-γ can increase the levels of GM-CSF to alter the differentiation of pDCs into cDCs in vivo. Therefore, we provide a novel regulatory mechanism underlying pregnancy-related immune tolerance that involves the balance of DC subsets, which may offer a new target for the prevention of human spontaneous abortion.

Insulin-like growth factor binding protein 7 modulates estrogen-induced trophoblast proliferation and invasion in HTR-8 and JEG-3 cells.

Previous research has reported that IGFBP7 functions as a tumor suppressor gene in different tumors, but its role in the trophoblast has not been elucidated. In this research, we studied the regulation mechanism of IGFBP7 in trophoblast proliferation and invasion in HTR-8 and JEG-3 cell lines. We found that IGFBP7 was abundantly expressed in normal human syncytiotrophoblast tissue samples but that this was lacking in hydatidiform moles. The proliferation and invasion capacities of HTR-8 and JEG-3 cells were significantly inhibited by recombinant IGFBP7. Estrogen (E2) stimulated the expression of IGFBP7 at a concentration of 5-10 ng/mL. This stimulation was inhibited by the estrogen receptor antagonist Fulvestrant (ICI182.780) and a TGFß-neutralizing antibody. In conclusion, our data reveals that estrogen stimulates the expression of IGFBP7 through estrogen receptors and TGFß. The expression of IGFBP7 could be stimulated by TGFß in a dose-dependent manner and inhibited by IFNγ in HTR-8 and JEG-3 cells. IGFBP7 could also inhibit the phosphorylation of ERK and the expression of PCNA, MMP2 and MMP9 in HTR-8 and JEG-3 cells. These findings suggest that IGFBP7 is a key regulator of E2-induced trophoblast proliferation and invasion.