Division of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea.
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
Biol Reprod. 2022 Jun 13;106(6):1159-1174. doi: 10.1093/biolre/ioac058.
The appropriate balance between pro-inflammatory and anti-inflammatory cytokines is important for the maternal immune tolerance during pregnancy in mammals. Among the various cytokines, interleukin (IL)-10 (IL10) plays an essential role in anti-inflammatory responses, while IL12 is involved in pro-inflammatory responses during pregnancy. However, the roles of IL10 and IL12 in the endometrium during pregnancy have not been studied in pigs. Thus, we investigated the expression of IL10, IL12 (IL12A and IL12B), and their receptors (IL10RA, IL10RB, IL12RB1, and IL12RB2) at the maternal-conceptus interface. IL10, IL12, and their receptors were expressed in the endometrium during the estrous cycle and pregnancy in a pregnancy stage-specific manner. During pregnancy, IL10 expression increased on Day 15, whereas the expression of IL12A and IL12B decreased after the implantation period. IL10 protein was localized to luminal epithelial (LE), stromal cells, and macrophages; IL10RA protein to LE, endothelial, stromal, and T cells; and IL10RB mRNA to LE cells in the endometrium. IL10 and IL10RA proteins and IL10RB mRNA were also localized to chorionic epithelial (CE) cells. In endometrial explants, the expression of IL10RA and IL10RB was induced by estradiol-17β, IL-1β, and/or interferon-γ. Heme oxygenase 1, an IL10-inducible factor, was expressed in the endometrium with the highest levels on Day 30 of pregnancy and was localized to LE and CE cells. These results in pigs suggest that conceptus-derived signals change the endometrial immune environment by regulating the expression of IL10 and IL10 receptors at the maternal-conceptus interface and that IL10 may provide anti-inflammatory conditions for the maternal immune tolerance.
在哺乳动物妊娠期间，促炎细胞因子和抗炎细胞因子之间的适当平衡对于母体免疫耐受至关重要。在各种细胞因子中，白细胞介素 (IL)-10 (IL10) 在抗炎反应中发挥重要作用，而 IL12 则参与妊娠期间的促炎反应。然而，在猪的子宫内膜中，IL10 和 IL12 的作用尚未得到研究。因此，我们研究了 IL10、IL12（IL12A 和 IL12B）及其受体（IL10RA、IL10RB、IL12RB1 和 IL12RB2）在母体-胚胎界面的表达。IL10、IL12 及其受体在发情周期和妊娠期间以妊娠阶段特异性的方式在子宫内膜中表达。在妊娠期间，IL10 的表达在第 15 天增加，而 IL12A 和 IL12B 的表达在植入期后下降。IL10 蛋白定位于腔上皮 (LE)、基质细胞和巨噬细胞；IL10RA 蛋白定位于 LE、内皮细胞、基质细胞和 T 细胞；而 IL10RB mRNA 定位于子宫内膜的 LE 细胞。IL10 和 IL10RA 蛋白和 IL10RB mRNA 也定位于绒毛膜上皮 (CE) 细胞。在子宫内膜外植体中，IL10RA 和 IL10RB 的表达受雌二醇-17β、IL-1β 和/或干扰素-γ诱导。IL10 诱导因子血红素加氧酶 1 在子宫内膜中表达，妊娠第 30 天表达水平最高，定位于 LE 和 CE 细胞。这些猪的研究结果表明，胚胎源性信号通过调节母胎界面的 IL10 和 IL10 受体的表达来改变子宫内膜免疫环境，而 IL10 可能为母体免疫耐受提供抗炎条件。
