Aghaeepour Nima, Ganio Edward A, Mcilwain David, Tsai Amy S, Tingle Martha, Van Gassen Sofie, Gaudilliere Dyani K, Baca Quentin, McNeil Leslie, Okada Robin, Ghaemi Mohammad S, Furman David, Wong Ronald J, Winn Virginia D, Druzin Maurice L, El-Sayed Yaser Y, Quaintance Cecele, Gibbs Ronald, Darmstadt Gary L, Shaw Gary M, Stevenson David K, Tibshirani Robert, Nolan Garry P, Lewis David B, Angst Martin S, Gaudilliere Brice
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94121, USA.
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94121, USA.
Sci Immunol. 2017 Sep 1;2(15). doi: 10.1126/sciimmunol.aan2946.
The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2-dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.
妊娠的维持依赖于精确调节的免疫适应。我们证明这些适应是精确计时的，反映了足月分娩女性的妊娠免疫时钟。使用质谱流式细胞术，在整个孕期收集的系列血样中对所有主要免疫细胞亚群的丰度和功能反应进行了定量。基于细胞信号的弹性网络（一种从弹性网络算法改编而来的正则化回归方法）被开发出来，以推断并前瞻性验证一个相互关联的免疫事件预测模型，该模型能准确捕捉妊娠的时间顺序。模型组件突出了现有知识，并揭示了以前未报道的生物学现象，包括白细胞介素-2依赖性STAT5ab信号通路在调节孕期T细胞功能中的关键作用。这些发现揭示了足月妊娠期间发生的免疫事件的精确时间，并提供了分析框架来识别与妊娠相关病理中涉及的免疫偏差。
