Abstract
Early-onset preeclampsia is a common obstetrical disease with a potential genetic background and is characterized by the predominance of Th1 immune response. However, although many studies investigated the immunological environment in preeclamptic patients, no information is available about the potential role of the TIGIT/CD226/CD112/CD155 immune checkpoint pathway. A total of 37 pregnant women diagnosed with early-onset preeclampsia and 36 control women with appropriately matched gestational age were enrolled in this study. From venous blood, mononuclear cells were isolated and stored in the freezer. Using multicolor flow cytometry T-, NK cell and monocyte subpopulations were determined. After characterization of the immune cell subsets, TIGIT, CD226, CD112, and CD155 surface expression and intracellular granzyme B content were determined by flow cytometer. Significantly decreased CD226 expression and increased CD112 and CD155 surface expression were detected in almost all investigated T-cell, NK cell, and monocyte subpopulations in women diagnosed with preeclampsia compared to the healthy group. Furthermore, reduced TIGIT and granzyme B expression were measured only in preeclamptic CD8+ T cells compared to healthy pregnant women. A decreased level of the activatory receptor CD226 in effector lymphocytes accompanied with an elevated surface presence of the CD112 and CD155 ligands in monocytes could promote the TIGIT/CD112 and/or TIGIT/CD155 ligation, which mediates inhibitory signals. We assume that the inhibition of the immune response via this immune checkpoint pathway might contribute to compensate for the Th1 predominance during early-onset preeclampsia.
Highlights
Lymphocyte and monocyte subsets were determined based on the gating strategy (Figure 1 and Figure 7)
Following the investigation of the receptor molecules, we examined the other side of the checkpoint pathway; according to a recent publication [37], we identified three different monocyte subpopulations and determined their CD122 and CD155 ligand expression
The role of the immune checkpoint molecules and pathways is to maintain the immunological balance between the pro- and anti-inflammatory responses/reactions
Summary
The incidence of the disease is increasing, especially in developing countries, and without proper health care can lead to preterm birth accompanied by fetal growth restriction [1]. The etiology of the disease is still unknown, but the overreaction of the expected maternal inflammation could lead to a restricted migration of the cytotrophoblast with endothelial injury. These processes can induce insufficient implantation and result from a small-sized placenta [2], which try to decompensate continuously when fetal growth is accelerated and leads to the appearance of the maternal symptoms [1]. Preeclampsia is characterized by maternal symptoms, which is, according to the International Society for the Biomedicines 2021, 9, 1608.
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