Habel Jennifer R, Nguyen Thi H O, Allen Lilith F, Hagen Ruth R, Kedzierski Lukasz, Allen E Kaitlynn, Jia Xiaoxiao, Li Shihan, Tarasova Ilariya, Minervina Anastasia A, Pogorelyy Mikhail V, Saunders Philippa M, Clatch Allison, Evrard Maximilien, Xu Calvin, Koay Hui-Fern, Khan Md Abdullah-Al-Kamran, de Alwis Natasha, Mackay Laura K, Barrow Alexander D, Douros Celia, Karapanagiotidis Theo, Nicholson Suellen, Bond Katherine, Williamson Deborah A, Lappas Martha, Walker Susan, Hannan Natalie J, Brooks Andrew G, Schroeder Jan, Crawford Jeremy Chase, Thomas Paul G, Rowntree Louise C, Kedzierska Katherine
Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Computational Sciences Initiative, Department of Immunology and Microbiology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
medRxiv. 2025 Mar 25:2025.03.24.25324489. doi: 10.1101/2025.03.24.25324489.
Human pregnancy presents a unique physiological state that allows for growth of an antigenically dissimilar foetus and requires specific adaptations of the immune system. The immune system plays an important role in establishing and maintaining successful pregnancy, yet deep understanding of immunological responses in pregnancy is lacking. To provide in-depth understanding of the immunological landscape of pregnancy, with a focus on NK cells, we used high-throughput cell surface proteome screening of >350 markers and scRNAseq with 130 CITE-seq antibodies to identify key differentially expressed molecules and investigated their potential roles in altered immunity. We identified skewing in NK cell subsets towards higher frequencies of CD56 cells caused by a reduced number of CD56 cells in the peripheral blood during pregnancy and provide evidence for a role of chemokine receptor, CX3CR1, in NK cell activation. In addition, we defined a new cytomegalovirus (CMV)-induced decidual NK cell population in CMV pregnancies with tissue-residency markers. Overall, our data provide fundamental knowledge into how NK cell immunity is altered in pregnancy, and key knowledge needed to inform vaccine and therapeutic strategies to manage infections or pregnancy complications.
人类妊娠呈现出一种独特的生理状态，它允许抗原性不同的胎儿生长，并且需要免疫系统进行特定的适应性调整。免疫系统在建立和维持成功妊娠方面发挥着重要作用，但目前仍缺乏对妊娠免疫反应的深入了解。为了深入了解妊娠的免疫格局，重点关注自然杀伤（NK）细胞，我们使用了对350多个标志物进行的高通量细胞表面蛋白质组筛选以及带有130种细胞索引转录组和表位测序（CITE-seq）抗体的单细胞RNA测序（scRNAseq）来鉴定关键的差异表达分子，并研究它们在免疫改变中的潜在作用。我们发现，由于孕期外周血中CD56⁻ NK细胞数量减少，导致NK细胞亚群向CD56⁺细胞的更高频率偏移，并为趋化因子受体CX3CR1在NK细胞激活中的作用提供了证据。此外，我们用组织驻留标志物定义了巨细胞病毒（CMV）感染妊娠中一种新的CMV诱导的蜕膜NK细胞群体。总体而言，我们的数据为孕期NK细胞免疫如何改变提供了基础知识，以及为制定管理感染或妊娠并发症的疫苗和治疗策略所需的关键知识。
