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

怀孕的哺乳动物必须对胎儿产生免疫耐受性。母体免疫系统对妊娠的适应是通过母体激素、免疫细胞和半同种异体胎儿/胎盘细胞之间的相互作用实现的。然而，这种母胎免疫串扰也对产妇健康产生了重大影响，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性。I型干扰素在调节对病毒感染和自身免疫性疾病的免疫反应中发挥核心作用。然而，关于怀孕和妊娠相关性激素对I型干扰素途径及其调控的影响，人们知之甚少。在这个项目中，我们将检验与怀孕相关的激素导致对病原体识别和炎症至关重要的先天免疫途径改变的假设。这些妊娠诱导的I型干扰素途径的变化可能导致对病毒感染的调节易感性，但也降低了一些自身免疫性疾病的严重程度。更好地了解怀孕、性激素和I型IFN之间的相互作用，对于指导新的治疗干预措施以改善孕妇的健康至关重要。

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.