Effect of leukemia inhibitory factor on immune checkpoint-related gene expression: a possible new window to overcome recurrent pregnancy loss and boost immune system tolerance

Abstract

Recurrent pregnancy loss (RPL) is an essential issue in reproductive science that affects 1–3% of women. Immune checkpoint molecules play crucial roles in successful pregnancies. This study investigates the effect of leukemia inhibitory factor (LIF) on immune checkpoint-related genes in abortion-prone mouse decidua. In this animal trial study, we used three groups of mice. The first group included CBA/J (F) × BALB/c (M) and CBA/J (F) × DBA/2J (M) without injection, in which PD-1 , PD-L1 , TIM-3 , Gal-9 , LAG-3 , Gal-3 , ST6GALNAC1 , LAIR1 , GITR , and VISTA gene expression were investigated in the decidua of mice on day 4 after vaginal plaque formation. The second and third groups included CBA/J (F) × BALB/c (M) without injection and CBA/J (F) × DBA/2J (M) with phosphate-buffered saline injection and DBA/2J (M) × CBA/ J (F) with 40 µg LIF on day 3 of pregnancy injected intraperitoneally. The second group was investigated on the 7th while the third was on the 14th day of pregnancy. On day 4, the expression of PD-1 and VISTA genes was lower, and the expression of TIM-3 , LAG-3 , LAIR-1 , and GITR genes was higher in the abortion-prone mice. LIF upregulated the expression levels of PD-1 and Gal-9 genes. On the 7th day of pregnancy, the expression of TIM-3 , Gal-3 , VISTA , LAIR-1 , and GITR genes increased on the 14th day of pregnancy. Based on our findings, LIF may modulate immune checkpoint-related gene expression in the abortion-prone mouse model. Further studies examining protein expression, immune cell-specific responses, and functional mechanisms are needed before considering translational applications.