Hormonal modulation of the Type I Interferon response during pregnancy: implications formaternal health and disease

怀孕的哺乳动物必须增强对胎儿的免疫耐受性。母体免疫系统对妊娠的适应是通过母体激素、免疫细胞和半异体胎儿/胎盘细胞之间的相互作用来实现的。然而，这种母婴免疫串扰也对孕产妇健康产生重大影响，包括多发性硬化症（MS）的改善，但也增加了对某些病毒感染的易感。I型ifn在病毒感染和自身免疫性疾病的免疫反应调节中发挥核心作用。然而，关于妊娠和妊娠相关性激素对I型IFN通路及其调控的影响知之甚少。在这个项目中，我们将测试怀孕相关激素导致对病原体识别和炎症至关重要的先天免疫途径变化的假设。这些妊娠引起的I型IFN通路的改变可能导致对病毒感染的易感性调节，但也降低了一些自身免疫性疾病的严重程度。更好地了解妊娠、性激素和I型干扰素之间的相互作用将是指导新的治疗干预措施以改善孕妇健康的关键。

Pregnant mammals have to mount immunological tolerance towards the fetus. Adaptation of the maternal immune system to pregnancy is achieved by the cross-talk between maternal hormones, immune cells and semiallogenic fetal/placental cells. However, this feto-maternal immune crosstalk also has significant consequences for maternal health, including amelioration of multiple sclerosis (MS), but also increased susceptibility to some viral infections. Type I IFNs play a central role in the regulation of both the immune response to viral infections and autoimmune diseases. However, little is known about the consequences of pregnancy and pregnancy-related sex hormones for the Type I IFN pathway and its regulation. In this project, we will test the hypothesis that pregnancy-related hormones lead to changes in innate immune pathways critical for pathogen recognition and inflammation. These pregnancy-induced changes of the Type I IFN pathway might result in modulated susceptibility to viral infections, but also a reduced severity of some autoimmune diseases. A better understanding of the interplay between pregnancy, sex hormones and Type I IFNs will be critical to guide novel therapeutic interventions to ameliorate the health of pregnant women.