Immune checkpoint for pregnancy.

Abstract

A successful pregnancy relies on the precise regulation of the maternal immune system to recognize and tolerate the allogeneic fetus, while simultaneously preventing infection. Immune checkpoint molecules (ICMs), such as programmed death receptor 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T cell immunoglobulin, and mucin-domain containing-3 (Tim-3), play critical roles in regulating the immune response during pregnancy. Emerging research highlights the therapeutic potential of targeting these molecules to restore the immune balance in complicated pregnancies. Understanding the dynamic regulation of ICMs during pregnancy may provide new insights into the pathogenesis of these conditions and offer novel approaches for clinical interventions. Here, we review the expression patterns and functions of key ICMs at the maternal-fetal interface, and their involvement in maintaining immune tolerance throughout gestation. Additionally, we describe the current understanding of immune checkpoint pathways in the pathogenesis of complicated pregnancies and discuss the potential for therapeutic targeting of these pathways in this setting.