Expression and significance of interferon-regulatory factor 4 at fetomaternal-interface

Abstract

Objective To investigate the expression and significance at interferon-regulatory factor 4 (IRF4) at fetomaternal-interface in pregnancy and abortion. Methods Pregnancy models were established in BALB/c mice. Immunohistochemistry was used to detect the IRF4 protein expression in uterine placenta tissue at 14.5 days of gestation. The spleen and uterine placenta tissues were harvested from unpregnant mice and those at 4.5, 8.5, 12.5 and 16.5 days of pregnancy, and were measured for IRF4 and RORγt mRNA levels by using real-time quantitative PCR (qPCR) . The correlation between IRF4 and RORγt mRNA levels was analyzed. A spontaneous abortion mouse model was established by mating female CBA/J mice and male DBA/2J mice, and a normal pregnancy control by mating female CAB/J mice with male BALB/c mice. qPCR and Western blotting were used to analyze the expression differences in IRF4, RORγt and IL-17 at the fetomaternal interface. Results IRF4 was mainly expressed in the lymphocytes of the fetomaternal interface. During pregnancy, the level of IRF4 in the fetomaternal interface showed a dynamic change, reaching the peak (1.92±0.12) on day 5 of gestation, and was significantly lower than those in unpregnant mice during the rest time points of gestation. The levels of IRF4 at 8.5, 12.5 and 16.5 days of gestation were 0.25±0.03, 0.03±0.01 and 0.10±0.005, respectively, compared with 1.00±0.04 in unpregant mice (P<0.05) , and were positively correlated with the level of RORγt (r2= 0.6968, P<0.05) . The mRNA and protein levels of IRF4 in spontaneous abortion group were significantly higher than those in normal pregnancy control group[ (1.41 ± 0.04) vs (1.00 ± 0.12) , P<0.05]. The mRNA levels of RORγt and IL-17 in spontaneous abortion group were also higher[RORγt: (2.01 ± 0.03) vs (1.00 ± 0.14) ; IL-17: (2.69 ± 0.20) vs (1.00 ± 0.09) (P<0.05) ]. Conclusion IRF4 may be playing an important role in the differentiation and functioning of Th17 cells through RORγt, and may participate in maternal immune regulation and affect the outcome of pregnancy. Key words: Interferon regulatory factor; Pregnancy outcome; Immunity; Th17 cells