TIGIT and CD155 as Immune-Modulator Receptor and Ligand on CD4 T cells in Preeclampsia Patients.

One of the main characteristics of preeclampsia (PE) is systemic inflammation. CD4 FoxP3 cells play a critical role in both fetomaternal tolerance and successful pregnancy. T-cell immunoglobulin, as well as immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT)/CD155 pathway, possesses critical parts in the development of normal pregnancy by promoting regulatory T (Treg) cells. However, in PE, the relationship between TIGIT/CD155 and Treg differentiation has not been entirely clarified. In the current report, we aimed to assess the frequency of TIGIT and CD155 expressing TCD4 cells in both PE and healthy pregnant women, as well as evaluating the amount of inflammatory and inhibitory cytokines at both mRNA and protein levels before and after blocking TIGIT and CD155. In the present report, 59 healthy, and 52 PE patients were designated to obtain their venous blood. The isolation of peripheral blood mononuclear cells (PBMCs) was performed from the blood samples, and PBMCs were then cultured in the RPMI1640 medium. The percentage of CD155 and TIGIT CD4 cells was assessed by flow cytometry in PBMCs. Cell culture supernatants were utilized to evaluate the secretory levels of transforming growth factor beta (TGF-β), interleukin (IL)-10, IL-17, tumor necrosis factor alpha (TNF-α), and IL-1 β, using enzyme-linked immunosorbent assay technique in pregnant women with or without PE both before and after blocking TIGIT and CD155. The mRNA expression of Foxp3, TIGIT, CD155, SHP-1, TGF-β, IL-10, IL-17, TNF-α, and IL-1β was also assessed by qRT-PCR in PBMCs before and after blocking TIGIT and CD155 in both populations. The data showed a significant decrease in the frequency of TIGIT CD4 and CD155 CD4 T cells in PE women, compared to the control group. Our results showed decreased protein and mRNA levels of TIGIT, CD155, IL-10, FOXP3, and SHP-1 in PE patients. In addition, significant improvements in the levels of IL-17, TNF-α, and IL-1β were observed in PE patients, as compared with the controls. However, blocking TIGIT and CD155 could increase these inflammatory cytokines and decrease anti-inflammatory cytokines. The data obtained in this report illustrated that there existed an imbalance between inflammatory and anti-inflammatory profiles, with an inflammatory status polarization, in PE patients. Additionally, TIGIT/CD155 showed a positive effect on immune regulation by activating ITIM, demonstrating the potential therapeutic value of the TIGIT/CD155 pathway in PE treatment. Also, using some proteins or materials that increased TIGIT/CD155 pathways activity and can be a therapeutic approach in PE.