HIF-1α-Deficiency in Myeloid Cells Leads to a Disturbed Accumulation of Myeloid Derived Suppressor Cells (MDSC) During Pregnancy and to an Increased Abortion Rate in Mice

Frontiers in Immunology
Natascha Köstlin-GilleChristian Gille

Abstract

Abortions are the most important reason for unintentional childlessness. During pregnancy, maternal immune cells are in close contact to cells of the semi-allogeneic fetus. Dysregulation of the maternal immune system leading to defective adaptation to pregnancy often plays a role in pathogenesis of abortions. Myeloid-derived suppressor cells (MDSC) are myeloid cells that suppress functions of other immune cells, especially T-cells, thereby negatively affecting diseases such as cancer, sepsis or trauma. They seem, however, also necessary for maintenance of maternal-fetal tolerance. Mechanisms regulating MDSC expansion and function during pregnancy are only incompletely understood. In tumor environment, hypoxia is crucial for MDSC accumulation and activation. Hypoxia is also important for early placenta and embryo development. Effects of hypoxia are mediated through hypoxia-inducible factor 1α (HIF-1α). In the present study we aimed to examine the role of HIF-1α in myeloid cells for MDSC accumulation and MDSC function during pregnancy and for pregnancy outcome. We therefore used a mouse model with targeted deletion of HIF-1α in myeloid cells (myeloid HIF-KO) and analyzed blood, spleens and uteri of pregnant mice at gestational da...Continue Reading

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Citations

May 18, 2020·American Journal of Reproductive Immunology : AJRI·Zi-Meng ZhengJun Shao
Nov 10, 2020·Frontiers in Immunology·Natascha Köstlin-Gille, Christian Gille
Aug 17, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Abdolreza OsaliAbdolreza Esmaeilzadeh
Jun 9, 2021·Reproductive Sciences·Dan LiYeling Wang
Jun 16, 2021·International Reviews of Immunology·Yi ZhangWei Yang

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
FCS

Software Mentioned

GraphPad Prism
GraphPad
CellQuest

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