Immune checkpoint molecules as regulators of immune tolerance in pregnancy
Abstract
The review presents current data on the immunoregulatory role of inhibitory receptors, which, together with ligands, are negative regulators of immune responses. The most studied molecules are CTLA-4 (CD152), PD-1 (CD279), Tim-3 (CD366), as well as Lag-3 (CD223), Tigit and VISTA. The interaction of checkpoint receptors with their ligands activates a number of mechanisms: it changes the ratio of Th1/Th2, Th17/Treg, and M1/M2 towards dominance of cells with regulatory activity; induces the generation of regulatory T-cells that suppress the proliferation of effector T-lymphocytes and stimulates the proliferation of decidual CD8+-T cells and the secretion of anti-inflammatory cytokines. Increased expression or co-expression of checkpoint molecules on T-lymphocytes leads to cell exhaustion, which significantly reduces the functional activity of T cells. According to modern research, inhibitory molecules play a significant role in maintaining a normal pregnancy. The review presents data on the expression of inhibitory molecules of decidual and peripheral T cells in all trimesters of pregnancy, which shows the essential importance of checkpoint receptors and ligands in the detection of tolerance to fetal alloantigens. At the same time, the onset of pregnancy is accompanied by an increase in the expression level of PD-1, CTLA-4, Tim-3 inhibitory molecules and their ligands on the decidual and peripheral cells, which affects the formation of physiological immunosuppression. The development of gestational complications, such as miscarriage and preeclampsia, is accompanied by impaired expression of checkpoint molecules both at the local and systemic levels.
Keywords:immune checkpoint molecules; PD-1; Tim-3;Lag-3 Tigit; VISTA; pregnancy; miscarriage; preeclampsia
Received 31.03.2023. Accepted 22.05.2023.
For citation: Khonina N.A., Pasman N.M., Chernykh E.R. Inhibitory molecules as regulators of immune tolerance during pregnancy. Immunologiya. 2023; 44 (4): 491–9. DOI: https://doi.org/10.33029/0206-4952-2023-44-4-491-499 (in Russian)
Funding. This study had no sponsor support.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. Writing the text – Khonina N.A., Pasman N.M.; editing – Chernykh E.R.
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