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Sci Immunol. 2017 Sep 1;2(15). pii: eaan2946. doi: 10.1126/sciimmunol.aan2946.

An immune clock of human pregnancy.

Author information

1
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94121, USA.
2
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94121, USA.
3
Department of Information Technology, Ghent University, and the Center for Inflammation Research, Ghent, Belgium.
4
Department of Surgery, Stanford University School of Medicine, Stanford, CA 94121, USA.
5
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
6
Institute for Immunogenetics, Jose de San Martin Clinical Hospital, National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
7
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94121, USA.
8
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94121, USA.
9
Departments of Biomedical Data Sciences and Statistics, Stanford University, Stanford, CA 94121, USA.
10
Division of Pediatric Immunology and Allergy, Stanford University School of Medicine, Stanford, CA 94121, USA.
11
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94121, USA. gbrice@stanford.edu.

Abstract

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.

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