title: Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.
abstract: Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4+and CD8+T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet+CD4+T cells, CD8+T cells, B cells, and CD56loCD16+NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes.
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Gabriela K
authors: 0000-0001-9703-2591
authors: GK
authors: Fragiadakis
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Quentin J
authors: QJ
authors: Baca
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Pier Federico
authors: PF
authors: Gherardini
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Edward A
authors: 0000-0002-1088-0377
authors: EA
authors: Ganio
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305.
authors: Dyani K
authors: DK
authors: Gaudilliere
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Martha
authors: M
authors: Tingle
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Hope L
authors: 0000-0002-7821-0126
authors: HL
authors: Lancero
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Leslie S
authors: LS
authors: McNeil
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Matthew H
authors: 0000-0002-5291-3819
authors: MH
authors: Spitzer
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.
authors: Ronald J
authors: 0000-0003-1205-6936
authors: RJ
authors: Wong
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.
authors: Gary M
authors: GM
authors: Shaw
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.
authors: Gary L
authors: GL
authors: Darmstadt
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305.
authors: Karl G
authors: KG
authors: Sylvester
authors: Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305; and.
authors: Virginia D
authors: VD
authors: Winn
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Brendan
authors: B
authors: Carvalho
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.|Division of Allergy, Immunology, and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305.
authors: David B
authors: DB
authors: Lewis
authors: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305.
authors: David K
authors: DK
authors: Stevenson
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Garry P
authors: GP
authors: Nolan
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Nima
authors: N
authors: Aghaeepour
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Martin S
authors: MS
authors: Angst
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305; gbrice@stanford.edu.
authors: Brice L
authors: 0000-0002-3475-5706
authors: BL
authors: Gaudilliere
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D011257:Pregnancy Proteins / Q000276:immunology; D050794:STAT1 Transcription Factor / Q000276:immunology
chemical_list: D011257:Pregnancy Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases