Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype
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- Natascha Köstlin
- *Department of Neonatology, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Kathrin Hofstädter
- *Department of Neonatology, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Anna-Lena Ostermeir
- *Department of Neonatology, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Bärbel Spring
- *Department of Neonatology, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Anja Leiber
- *Department of Neonatology, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Susanne Haen
- †Department of Pathology, University Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Harald Abele
- ‡Department of Obstetrics and Gynecology, University Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Peter Bauer
- §Institute of Medical Genetics and Applied Genomics, University Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Jürgen Pollheimer
- ¶Department of Obstetrics and Fetal-Maternal Medicine, Medical University of Vienna, 1090 Vienna, Austria; and
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- Dominik Hartl
- ‖Department of Pediatrics I, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany
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- Christian F. Poets
- *Department of Neonatology, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany;
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- Christian Gille
- *Department of Neonatology, University Children’s Hospital Tuebingen, 72076 Tuebingen, Germany;
抄録
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 196 (3), 1132-1145, 2016-02-01
The American Association of Immunologists
