Continuous activation of polymorphonuclear myeloid-derived suppressor cells during pregnancy is critical for fetal development

Shi, Mengyu; Chen, Ziyang; Chen, Meiqi; Liu, Jingping; Li, Jing; Xing, Zhe; Zhang, Xiaogang; Lv, Shuaijun; Li, Xinyao; Zuo, Shaowen; Feng, Shi; Lin, Ying; Xiao, Gang; Wang, Liping; He, Yumei

doi:10.1038/s41423-021-00704-w

Cited by 16 publications

(5 citation statements)

References 69 publications

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“…PBMCs were isolated from healthy individuals as described previously by Shi et al (46). After cell sorting, purified human ILC2s were stimulated (at an initial density of approximately 5.0 × 10 3 cells/200 µL in 96-well round-bottom plates) with recombinant human (rh)IL-2 (20 ng/mL), rhIL-7 (20 ng/mL), and/or rhIL-33 (20 ng/ml) in the presence or absence of increasing doses of BQ123 (100 µM), ET-1 (500 ng/mL), U0126 (20 µM) or MG132 (20 µM) for 3 days.…”

Section: Human Ilc2 Functionmentioning

confidence: 99%

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

et al. 2022

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Allergic airway inflammation is a universal airway disease that is driven by hyperresponsiveness to inhaled allergens. Group 2 innate lymphoid cells (ILC2s) produce copious amounts of type 2 cytokines, which lead to allergic airway inflammation. Here, we discovered that both peripheral blood of human and mouse lung ILC2s express the endothelin-A receptor (ETAR), and the expression level of ETAR was dramatically induced upon interleukin-33 (IL-33) treatment. Subsequently, both preventive and therapeutic effects of BQ123, an ETAR antagonist, on allergic airway inflammation were observed, which were associated with decreased proliferation and type 2 cytokine productions by ILC2s. Furthermore, ILC2s from BQ123 treatment were found to be functionally impaired in response to an interleukin IL-33 challenged. And BQ123 treatment also affected the phosphorylation level of the extracellular signal-regulated kinase (ERK), as well as the level of GATA binding protein 3 (GATA3) in activated ILC2s. Interestingly, after BQ123 treatment, both mouse and human ILC2s in vitro exhibited decreased function and downregulation of ERK signaling and GATA3 stability. These observations imply that ETAR is an important regulator of ILC2 function and may be involved in ILC2-driven pulmonary inflammation. Therefore, blocking ETAR may be a promising therapeutic strategy for allergic airway inflammation.

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Section: Human Ilc2 Functionmentioning

confidence: 99%

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

et al. 2022

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“…As mentioned previously, G-MDSCs are observed in all stages of pregnancy and are accompanied by high cellular levels of Arg-1 and ROS activity; however, patients with IUGR exhibit a significantly lower suppressive activity. Moreover, the frequency of G-MDSCs is negatively correlated with adverse outcomes in newborns from pregnancies with IUGR ( 120 ). The MDSC ratio and serum Arg-1 levels in patients with PE are much lower than those in healthy pregnant women ( 111 ).…”

Section: Mdscs During Pregnancymentioning

confidence: 99%

Myeloidderived suppressor cells: Escorts at the maternal–fetal interface

Pang

et al. 2023

Front. Immunol.

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Myeloid-derived suppressor cells (MDSCs) are a novel heterogenous group of immunosuppressive cells derived from myeloid progenitors. Their role is well known in tumors and autoimmune diseases. In recent years, the role and function of MDSCs during reproduction have attracted increasing attention. Improving the understanding of their strong association with recurrent implantation failure, pathological pregnancy, and neonatal health has become a focus area in research. In this review, we focus on the interaction between MDSCs and other cell types (immune and non-immune cells) from embryo implantation to postpartum. Furthermore, we discuss the molecular mechanisms that could facilitate the therapeutic targeting of MDSCs. Therefore, this review intends to encourage further research in the field of maternal–fetal interface immunity in order to identify probable pathways driving the accumulation of MDSCs and to effectively target their ability to promote embryo implantation, reduce pathological pregnancy, and increase neonatal health.

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“…24 The elevation in peripheral blood γδT cells with cytotoxic potential has been shown to be associated with RSA. 25 Myeloid-derived suppressor cells (MDSCs), also known as CD11b + Gr-1 + cells, 26 are an important group of immunosuppressive cells at the maternal-fetal interface, 27 which are involved in maternal-fetal immune tolerance, placental development, and fetal growth during pregnancy. 27,28 Moreover, a study has opined that the adoptive transfer of MDSCs could improve murine pregnancy outcomes.…”

Section: Introductionmentioning

confidence: 99%

Kisspeptin prevents pregnancy loss by modulating the immune microenvironment at the maternal‐fetal interface in recurrent spontaneous abortion

Yang,

Song,

et al. 2024

American J Rep Immunol

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ProblemImmune factors are crucial in the development of recurrent spontaneous abortion (RSA). This study aimed to investigate whether kisspeptin regulates immune cells at the maternal‐fetal interface and whether G protein‐coupled receptor 54 (GPR54) is involved in this process, through which it contributes to the pathogenesis of RSA.Method of studyNormal pregnancy (NP) (CBA/J × BALB/c) and RSA (CBA/J × DBA/2) mouse models were established. NP mice received tail vein injections of PBS and KP234 (blocker of kisspeptin receptor), whereas RSA mice received PBS and KP10 (active fragment of kisspeptin). The changes in immune cells in mouse spleen and uterus were assessed using flow cytometry and immunofluorescence. The expression of critical cytokines was examined by flow cytometry, ELISA, Western blotting, and qPCR. Immunofluorescence was employed to detect the coexpression of FOXP3 and GPR54.ResultsThe findings revealed that the proportion of Treg cells, MDSCs, and M2 macrophages in RSA mice was lower than that in NP mice, but it increased following the tail vein injection of KP10. Conversely, the proportion of these cells was reduced in NP mice after the injection of KP234. However, the trend of γδT cell proportion change is contrary to these cells. Furthermore, FOXP3 and GPR54 were coexpressed in mouse spleen and uterus Treg cells as well as in the human decidua samples.ConclusionOur results suggest that kisspeptin potentially participates in the pathogenesis of RSA by influencing immune cell subsets at the maternal‐fetal interface, including Treg cells, MDSC cells, γδT cells, and M2 macrophages.

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Continuous activation of polymorphonuclear myeloid-derived suppressor cells during pregnancy is critical for fetal development

Cited by 16 publications

References 69 publications

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

Myeloidderived suppressor cells: Escorts at the maternal–fetal interface

Kisspeptin prevents pregnancy loss by modulating the immune microenvironment at the maternal‐fetal interface in recurrent spontaneous abortion

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