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

怀孕期间 I 型干扰素反应的激素调节：对孕妇健康和疾病的影响

• 批准号: 269121614
• 负责人: Professor Dr. Marcus Altfeld
• 金额: --
• 依托单位: Leibniz-Institut für Virologie (LIV)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/269121614?language=en
• 关键词: Hormonal; modulation; Type; Interferon; response

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.

怀孕的哺乳动物必须对胎儿产生免疫耐受。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，这种胎儿-母体免疫串扰也对母体健康有显著影响，包括改善多发性硬化症（MS），但也增加了对某些病毒感染的易感性。I型IFN在调节对病毒感染和自身免疫性疾病的免疫应答中起核心作用。然而，很少有人知道妊娠和妊娠相关性激素的I型干扰素途径及其调节的后果。在这个项目中，我们将测试怀孕相关激素导致先天免疫途径的变化对病原体识别和炎症至关重要的假设。这些妊娠诱导的I型IFN途径的变化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。更好地了解怀孕，性激素和I型干扰素之间的相互作用将是至关重要的，以指导新的治疗干预措施，以改善孕妇的健康。