The transdifferentiation of regulatory T and Th17 cells in autoimmune/inflammatory diseases and its potential implications in pregnancy complications.

In the past decades, studies have shown that a balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells plays a major role in autoimmune/inflammatory diseases as well as pregnancy complications. Decreased number and function of Tregs, and increased number of Th17 cells which often have an opposed effect of Tregs, are associated with these conditions. Recently, the plasticity of Tregs and Th17 cells has been reported to be involved in the pathogenesis of autoimmune/inflammatory diseases. Hence, we summarize the current knowledge of Tregs and Th17 cells plasticity with an emphasis on their reciprocal transdifferentiation in autoimmune/inflammatory diseases. Moreover, the regulators of the Tregs-to-Th17 cells transdifferentiation are discussed as well. Finally, by reviewing the immuno-inflammatory status of pregnancy complications, such as preeclampsia and unexplained recurrent pregnancy losses, a possibility of Tregs-to-Th17 cells transdifferentiation as an underlying immune-pathology of these conditions is discussed.

What are the roles of macrophages and monocytes in human pregnancy?

During pregnancy, the maternal immune system is challenged by the semi-allogeneic fetus, which leads to systemic and local immunity. Systemic immunity, including enhanced innate immunity with increased activation of monocytes, is induced by various placental factors. Maternal immune adaptations are most evident at the feto-maternal interface, where macrophages are enriched and communicate with various decidual leukocytes. These cells are not only contributing to the protection of the growing fetus from microorganisms, but also aiding placental development by promoting trophoblast invasion and spiral artery remodeling, and the parturition process. Thus, monocytes and macrophages concurrently play important roles throughout the trimesters. Dysregulation of these cells may thus lead to pregnancy complications, such as pre-eclampsia and preterm labor. In this review, monocytes and macrophage subsets and their roles in normal and pathological pregnancies are reviewed.

Morphological Changes and Expression of Cytokine After Local Endometrial Injury in a Mouse Model.

OBJECTIVE: To establish a mouse model for endometrial injury and determine the underlying mechanism regarding its favorable effect on embryo implantation. STUDY DESIGN: Female Kunming mice were randomly allocated into 4 groups: group I, normal control; group II, injury procedure control; and group III and group IV, the mice being scratched with a blunt syringe on the right uterine horn or both, respectively. All the mice were mated with the males during the next estrus phase. The number of implanted embryos on each side of uterus was calculated on day 8 of pregnancy. The endometrial samples were taken on day 4 of pregnancy, and the local morphological changes and cytokine expressions were examined. RESULTS: Compared to group II, our results showed that in group IV (1) there were significantly higher numbers of implanted embryos, (2) the endometrial glands and vasculatures in stroma were obviously increased and the pinopodes were abundant and well developed, and (3) the local levels of cytokines leukemia inhibitory factor (LIF) and oncostatin M (OSM) messenger RNA and protein expression were significantly increased. CONCLUSIONS: Local mechanical injury on mouse uteri enhanced endometrial receptivity and improved embryo implantation, which were correlated with the characteristic changes in endometrial morphology and the upregulation of LIF and OSM gene and protein expression.

Recent Insight into the Role of the PD-1/PD-L1 Pathway in Feto-Maternal Tolerance and Pregnancy.

Pregnancy presents a great challenge to the maternal immune system. Given that maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to serve a central function in altering the maternal immune responses. Regulatory T cells (Tregs) and the PD-1/PD-L1 pathway are both critical in controlling the immune responses. Recent studies have proved the critical function of the PD-1/PD-L1 pathway in regulating the T-cell homeostasis and the peripheral tolerance through promoting the development and function of Tregs, and inhibiting the activation of effector T cells. The function of the PD-1/PD-L1 pathway in feto-maternal interface and pregnancy has been investigated in human and animal models of pregnancy. In this review, we provide recent insight into the role of the PD-1/PD-L1 pathway in regulating T-cell homeostasis, maternal tolerance, and pregnancy-related complications as well as its possible applicability in clinical immunotherapy.