The regular distribution and expression pattern of immunosuppressive cytokine IL-35 in mouse uterus during early...

Cytokines within the uterus are critical in the maternal-fetal immune regulation. Immunosuppressive cytokine IL-35 was recently discovered inhibitory cytokine, which were pivotal in the establishment of immune tolerance against self-antigens and antigens encountered in foreign implantation. In order to analyze the role of IL-35 in maternal-fetal immune tolerance, the expression patterns of IL-35 in mouse endometrium were studied during early pregnancy by immunohistochemistry, ELISA and quantitative real-time PCR. As results, we found that IL-35 positive cells in the uterus showed significant distribution difference after fetal implantation, which mainly distributed in luminal epithelium and glandular epithelium of mouse uterus from gestational day 1 to 2, and glandular epithelium and stroma from gestational day 4 to 7. The number of positive cells, immunoreactive scores, protein and mRNA expression of IL-35 showed firstly increased and then decreased with the increase of pregnancy day. The largest contents of IL-35 in the uterus were detected on gestational day 4. Compared with non-pregnant mice, pregnant mice showed the significantly increased mRNA expression of Ebi3 (Epstein-Barr virus-induced gene 3, IL-35 subunit) in the endometrium on gestational day 2 and the highest level of expression on gestational day 4. The mRNA expression of p35 (IL-35 subunit) was significantly lower than that of Ebi3 gene and showed the inconsistent change from gestational day 5 to 7. However, the significant correlation existed between the immunohistochemical expression, contents and mRNA expression of IL-35. These results indicated that IL-35 contributed to the establishment and maintenance of maternal-fetal tolerance during early pregnancy.