Myeloid-Derived Suppressor Cells in Pregnancy and the Neonatal Period

Köstlin-Gille, Natascha; Gille, Christian

doi:10.3389/fimmu.2020.584712

Cited by 35 publications

(26 citation statements)

References 59 publications

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“…G‐MDSCs also express granulocytic lineage markers CD15 and/or CD66b, whereas M‐MDSCs express the monocytic antigen CD14 [ 93 ]. In mice, GR‐MDSCs are defined as CD11b + /Ly6G + /Ly6C lo and MO‐MDSC as CD11b + /Ly6G − /Ly6C hi cells [ 94 ]. G‐MDSCs can be distinguished from mature neutrophils by their lower density and their sedimentation with mononuclear cells following density gradient centrifugation.…”

Section: The Cross‐talk Between Neutrophils and T Cellsmentioning

confidence: 99%

Neutrophils in pregnancy: New insights into innate and adaptive immune regulation

2021

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The immunology of pregnancy has been the focus of many studies to better understand how the mother is able to tolerate the presence of a semi‐allogeneic fetus. Far from the initial view of pregnancy as a state of immunosuppression, successful fetal development from implantation to birth is now known to be under the control of an intricate balance of immune cells. The balance between pro‐inflammatory functions used to promote embryo implantation and placental development and immunosuppressive activity to maintain maternal tolerance of the fetus is an immunological phenotype unique to pregnancy, which is dependent on the time of gestation. Neutrophils are one of a host of innate immune cells detected at the maternal–fetal interface, but very little is known of their function. In this review, we explore the emerging functions of neutrophils during pregnancy and their interactions with and regulation of T cells, a key adaptive immune cell population essential for the establishment of fetal–maternal tolerance.

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Section: The Cross‐talk Between Neutrophils and T Cellsmentioning

confidence: 99%

Neutrophils in pregnancy: New insights into innate and adaptive immune regulation

2021

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“…Both, systemically and locally in the uterus, we observed a strong increase in MDSC in WT but not in Qa-2mice. The accumulation of MDSC and its relevance for successful pregnancy has been described previously in different mouse models (reviewed in 37 ). However, all these studies focused on early-to mid-gestation, showing that depletion of MDSC in early gestation or genetically determined decreased MDSC accumulation at E10.5 led to complete gestation failure 16 or increased abortion rates 15,17 .…”

Section: Discussionmentioning

confidence: 74%

Human leucocyte antigen G (HLA-G) and its murine homologue Qa-2 protect from pregnancy loss

Dietz¹,

Schwarz²,

Velić³

et al. 2021

Preprint

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During pregnancy, the maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. The MHC-Ib molecule HLA-G is well known to mediate immunological tolerance. However, no in-vivo studies have yet demonstrated a beneficial role of HLA-G for pregnancy success. Myeloid derived suppressor cells (MDSC) are suppressively acting immune cells accumulating during pregnancy and mediating maternal-fetal tolerance. Here, we analyzed the impact of Qa-2, the murine homologue to HLA-G, on pregnancy outcome in vivo. We demonstrate that lack of Qa-2 led to intrauterine growth restriction and increased abortion rates especially in late pregnancy accompanied by changes in uterine gene expression, altered spiral artery remodeling and protein aggregation in trophoblast cells indicating a preeclampsia-like phenotype. Furthermore, lack of Qa-2 caused decreased accumulation of MDSC and impaired MDSC function. Lastly, we show that application of sHLA-G reduced abortion rates in Qa-2 deficient mice by inducing MDSC. Our results highlight the importance of an interaction between HLA-G and MDSC for pregnancy success and the therapeutic potential of HLA-G for the treatment of immunological pregnancy complications.

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Section: Discussionmentioning

confidence: 98%

Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome

et al. 2022

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During pregnancy, maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. In the present study we analyzed the impact of the murine MHC class Ib molecule Qa-2 on pregnancy outcome in vivo. We demonstrate that lack of Qa-2 led to intrauterine growth restriction and increased abortion rates especially in late pregnancy accompanied by a disturbed trophoblast invasion and altered spiral artery remodeling as well as protein aggregation in trophoblast cells indicating a preeclampsia-like phenotype. Furthermore, lack of Qa-2 caused imbalanced immunological adaptation to pregnancy with altered immune cell and especially T-cell homeostasis, reduced Treg numbers and decreased accumulation and functional activation of myeloid-derived suppressor cells. Lastly, we show that application of sHLA-G reduced abortion rates in Qa-2 deficient mice by inducing MDSC. Our results highlight the importance of an interaction between HLA-G and MDSC for pregnancy success and the therapeutic potential of HLA-G for treatment of immunological pregnancy complications.

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Myeloid-Derived Suppressor Cells in Pregnancy and the Neonatal Period

Cited by 35 publications

References 59 publications

Neutrophils in pregnancy: New insights into innate and adaptive immune regulation

Neutrophils in pregnancy: New insights into innate and adaptive immune regulation

Human leucocyte antigen G (HLA-G) and its murine homologue Qa-2 protect from pregnancy loss

Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome

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