Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype.
Natascha KöstlinKathrin HofstädterAnna-Lena OstermeirBärbel SpringAnja LeiberSusanne HaenHarald AbelePeter BauerJürgen PollheimerDominik HartlChristian F PoetsChristian GillePublished in: Journal of immunology (Baltimore, Md. : 1950) (2015)
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.
Keyphrases
- pregnancy outcomes
- induced apoptosis
- pregnant women
- cord blood
- cell cycle arrest
- preterm birth
- endothelial cells
- peripheral blood
- gestational age
- birth weight
- immune response
- poor prognosis
- endoplasmic reticulum stress
- oxidative stress
- body mass index
- risk factors
- nitric oxide
- low birth weight
- cell proliferation
- induced pluripotent stem cells
- risk assessment