title: Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype.
abstract: Tolerance induction toward the semiallogeneic fetus is crucial to enable a successful pregnancy; its failure is associated with abortion or preterm delivery. Skewing T cell differentiation toward a Th2-dominated phenotype seems to be pivotal in maternal immune adaption, yet underlying mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that mediate T cell suppression and are increased in cord blood of healthy newborns and in peripheral blood of pregnant women. In this study, we demonstrate that granulocytic MDSCs (GR-MDSCs) accumulate in human placenta of healthy pregnancies but are diminished in patients with spontaneous abortions. Placental GR-MDSCs effectively suppressed T cell responses by expression of arginase I and production of reactive oxygen species and were activated at the maternal-fetal interface through interaction with trophoblast cells. Furthermore, GR-MDSCs isolated from placenta polarized CD4(+) T cells toward a Th2 cytokine response. These results highlight a potential role of GR-MDSCs in inducing and maintaining maternal-fetal tolerance and suggest them as a promising target for therapeutic manipulation of pregnancy complications.
authors.affiliation: Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Natascha
authors.initials: N
authors.lastname: Köstlin
authors.affiliation: Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Kathrin
authors.identifier: http://orcid.org/0000-0002-3412-7427
authors.initials: K
authors.lastname: Hofstädter
authors.affiliation: Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Ostermeir
authors.affiliation: Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Bärbel
authors.initials: B
authors.lastname: Spring
authors.affiliation: Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Anja
authors.identifier: http://orcid.org/0000-0001-6140-6854
authors.initials: A
authors.lastname: Leiber
authors.affiliation: Department of Pathology, University Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Susanne
authors.initials: S
authors.lastname: Haen
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Harald
authors.initials: H
authors.lastname: Abele
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.affiliation: Department of Obstetrics and Fetal-Maternal Medicine, Medical University of Vienna, 1090 Vienna, Austria; and.
authors.forename: Jürgen
authors.identifier: http://orcid.org/0000-0001-8440-5221
authors.initials: J
authors.lastname: Pollheimer
authors.affiliation: Department of Pediatrics I, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.affiliation: Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany;
authors.forename: Christian F
authors.initials: CF
authors.lastname: Poets
authors.affiliation: Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany; christian.gille@med.uni-tuebingen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Gille
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology; D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D022423:Myeloid Cells / Q000276:immunology; D010641:Phenotype; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult