Reduced Myeloid-derived Suppressor Cells in the Blood and Endometrium is Associated with Early Miscarriage

Nair, Rohini R.; Sinha, Pratima; Khanna, Anuradha; Singh, Kiran

doi:10.1111/aji.12351

Cited by 74 publications

(74 citation statements)

References 47 publications

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“…These results parallel data from others showing an enrichment of Tregs in human decidua and an association between diminished Treg accumulation and pregnancy failure (32,34,35). Recently, reduced MDSCs in peripheral blood of patients with early miscarriage and a depletion of MDSCs leading to pregnancy failure in mice have also been shown (36,37). Taken together, our results add new aspects of MDSC biology in human pregnancy as being crucial during physiological conditions, that is, in human pregnancy, and point again toward a role for GRMDSCs in protecting the fetus from immune rejection.…”

Section: Discussionsupporting

confidence: 89%

“…Because CD66b staining cannot distinguish between immature GR-MDSCs with suppressive capacities and mature granulocytes, these results have to be viewed with caution. A recent study on MDSCs in early pregnancy using CD33 as a marker for MDSCs found a diffuse distribution of CD33 + cells in the endometrium (36). Similar to CD66b, CD33 is not specific for MDSCs but is also expressed on granulocytes and monocytes, so that to date no method exists to clearly identify the exact localization of MDSCs at the maternal-fetal interface.…”

Section: Discussionmentioning

confidence: 99%

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Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Köstlin

Hofstädter

Ostermeir

et al. 2016

The Journal of Immunology

101

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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.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Köstlin

Hofstädter

Ostermeir

et al. 2016

The Journal of Immunology

101

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“…In both mice and patients exacerbation of allergy-induced asthma is associated with diminished immune suppressive function of Gr-MDSC [110]. Recent studies also show a correlation between reduced levels of MDSC and miscarriage [111, 112], suggesting that MDSC may also be implicated in normal pregnancies. Therefore, MDSC may play a critical role in combating autoimmune and allergic reactions and have the potential to be exploited as therapeutic agents for multiple diseases involving harmful immune responses.…”

Section: Mdsc May Be Useful For Inducing Tolerance In Pathologicamentioning

confidence: 99%

Tolerance and immune suppression in the tumor microenvironment

Ostrand‐Rosenberg

2016

Cellular Immunology

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The concept of immunological tolerance has guided and permeated much of modern immunology. Ray Owen’s ground-breaking observations in twin cattle provided the first mechanistic explanation for tolerance to self-molecules and established tolerance as a beneficial process that protects the host against autoreactivity. However, his studies also opened the door to understanding that tolerance may be detrimental, such as occurs when cancer cells induce tolerance/immune suppression resulting in inhibition of anti-tumor immunity. This article briefly traces the early history of the field of tumor immunology with respect to tolerance, and then focuses on a relatively recently identified population of cells called myeloid-derived suppressor cells (MDSC). MDSC are instrumental in causing tolerance/immune suppression in individuals with cancer. They are present in most individuals with cancer and because of their potent immune suppressive activity are a major deterrent to natural anti-tumor immunity and a significant obstacle to immunotherapy.

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“…MDSCs, however, did not follow control levels on day 2 of pregnancy. In this case, control mice showed a significant increase in MDSC levels (P < 0.0001) between days 0 and 2 of pregnancy), which could probably ensure the development of the required immunosuppressive state (Nair et al 2015, Zhao et al 2016, while l-Cn-treated mice failed to further increase these levels (P = 0.018, Figure 5 Effect of in vivo l-Cn treatment on ovarian histology. Superovulated female mice received daily injections of 2.5 mg l-Cn for 5 or 7 days, caged with males and ovaries were isolated 18 h post-hCG injection on day 0 of pregnancy.…”

Section: Maternal Systemic Immunity Upon L-cn Treatmentmentioning

confidence: 96%

l-Carnitine affects preimplantation embryo development toward infertility in mice

et al. 2016

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Abstractl-Carnitine (l-Cn), despite the beneficial role as energy-generating substance delivering long-chain fatty acids to the β-oxidation pathway in mitochondria, has been accused to cause an endometriosis-like state to BALB/c mice manifested by increased inflammatory cytokines in serum and peritoneal fluid, accumulation of immune cells in the peritoneal cavity and uterine walls and most importantly, correlating to infertility. Exploring this type of infertility, the effect of l-Cn on preimplantation embryo development, ovarian integrity and systemic maternal immunity was studied. Using nonlinear microscopy analysis, which was shown to be a powerful tool for determining embryo quality by quantitatively estimating the lipid body (LB) content of the cells, it was shown that in vitro and in vivo administration of l-Cn significantly decreased LB mean area in zygotes. Daily intraperitoneal administration of 2.5 mg l-Cn for 3, 4 and 7 days to mice significantly decreased the percent of normal zygotes. However, only the 7-day treatment persisted by affecting 2-and 8-cell stage embryos, while almost abolishing blastocyst development. Such effects were accompanied by abnormal ovarian histology, showing increased numbers of corpora luteus and elevated progesterone concentration in the serum. In addition, it was shown that the 7-day l-Cn treatment pushed maternal systemic immunity toward inflammation and immunosuppression by increasing CD11b-, CD25-and CD11bGr1-positive cells in spleen, which opposed the necessity for immunostimulation at these early stages of pregnancy. In conclusion, the results presented here demonstrated that elevated doses of l-Cn affect early stages of embryo development, leading to infertility.Reproduction (2016) 152 283-291

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Reduced Myeloid-derived Suppressor Cells in the Blood and Endometrium is Associated with Early Miscarriage

Cited by 74 publications

References 47 publications

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype

Tolerance and immune suppression in the tumor microenvironment

l-Carnitine affects preimplantation embryo development toward infertility in mice

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