Multiomic immune clockworks of pregnancy
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REVIEW
Multiomic immune clockworks of pregnancy Laura S. Peterson 1 & Ina A. Stelzer 2 & Amy S. Tsai 2 & Mohammad S. Ghaemi 2 & Xiaoyuan Han 2 & Kazuo Ando 2 & Virginia D. Winn 3 & Nadine R. Martinez 3 & Kevin Contrepois 4,8 & Mira N. Moufarrej 5 & Stephen Quake 5 & David A. Relman 6,7 & Michael P. Snyder 8 & Gary M. Shaw 1 & David K. Stevenson 1 & Ronald J. Wong 1 & Petra Arck 9 & Martin S. Angst 2 & Nima Aghaeepour 2 & Brice Gaudilliere 2 Received: 26 July 2019 / Accepted: 31 October 2019 # The Author(s) 2019
Abstract Preterm birth is the leading cause of mortality in children under the age of five worldwide. Despite major efforts, we still lack the ability to accurately predict and effectively prevent preterm birth. While multiple factors contribute to preterm labor, dysregulations of immunological adaptations required for the maintenance of a healthy pregnancy is at its pathophysiological core. Consequently, a precise understanding of these chronologically paced immune adaptations and of the biological pacemakers that synchronize the pregnancy “immune clock” is a critical first step towards identifying deviations that are hallmarks of peterm birth. Here, we will review key elements of the fetal, placental, and maternal pacemakers that program the immune clock of pregnancy. We will then emphasize multiomic studies that enable a more integrated view of pregnancy-related immune adaptations. Such multiomic assessments can strengthen the biological plausibility of immunological findings and increase the power of biological signatures predictive of preterm birth Keywords Pregnancy . Preterm birth . Prematurity . parturition . multiomics . Immunology . Cytomics . Transcriptomics . Proteomics . Metabolomics . Microbiome . Mass cytometry
Introduction For the establishment, maintenance, and completion of mammalian pregnancy, the maternal immune system must adhere to a precise schedule. During 9 months, dynamic local and
systemic immune changes occur that confer tolerance to the semi-allogenic fetus while protecting the mother against invading pathogens. The appropriate execution of these important events requires a tightly regulated immunologic timeline governed by a complex system of immune pacemakers.
Martin S. Angst, Nima Aghaeepour, and Brice Gaudilliere are co-senior authors. This article is a contribution to the special issue on Preterm birth: Pathogenesis and clinical consequences revisited - Guest Editors: Anke Diemert and Petra Arck * Brice Gaudilliere [email protected] 1
2
Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA Department of Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA
3
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA
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Stanford Metabolic Health Center, Stanford University School of Medicine, Stanford, CA, USA
5
Department of Bioengineering, Stanford University School of Engineering, Stanford, CA, USA
6
Dep
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