Journal
SCIENCE IMMUNOLOGY
Volume 2, Issue 15, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aan2946
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Funding
- March of Dimes Prematurity Research Center at Stanford
- Bill and Melinda Gates Foundation [OPP1112382]
- Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University
- NIH [1K23GM111657-03, HHSF223201210194C, 5R01AI10012104, U19AI057229, 1U19AI100627]
- Ann Schreiber Mentored Investigator Award from the Ovarian Cancer Research Fund [OCRF 292495]
- Canadian Institute of Health Research (CIHR) Postdoctoral Fellowship [CIHR 321510]
- International Society for Advancement of Cytometry Scholarship
- Stanford Child Health Research Institute
- Mary L. Johnson Research Fund
- Christopher Hess Research Fund
- Agency for Innovation by Science and Technology in Flanders
- U.S. Food and Drug Administration [HHSF223201210194C]
- Bill and Melinda Gates Foundation [OPP1112382] Funding Source: Bill and Melinda Gates Foundation
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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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