Granulocytic myeloid-derived suppressor cells maintain feto-maternal tolerance by inducing Foxp3 expression in CD4<sup>+</sup>CD25<sup>−</sup>T cells by activation of the TGF-β/β-catenin pathway

Kang, Xiaomin; Zhang, Xiaoxin; Liu, Zhilan; Xu, Haijing; Wang, Tongfei; He, Lin; Zhao, Aimin

doi:10.1093/molehr/gaw026

Cited by 66 publications

(68 citation statements)

References 48 publications

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“…Consistent with the published data (Kang et al, , ; Sinha et al, ; A.‐M. Zhao et al, ), our recent studies (unpublished) have confirmed that MDSCs at the mouse maternal–fetal interface is critically involved in the maternal–fetal immunotolerance, and the reduction in the number of MDSCs and decline in their function may lead to the loss of pregnancy.…”

Section: Introductionsupporting

confidence: 91%

“…Several studies have shown that the accumulation and activation of MDSC are correlated with a successful pregnancy. For instance, it was found that MDSCs percentage is increased in the blood and the placenta of pregnant women (Kang et al, ; Kostlin et al, ). Furthermore, reduced levels of suppressive monocytes in the blood and endometrium in both mice and women are associated with higher incidences of early miscarriage (Nair, Sinha, Khanna, & Singh, ; H. Zhao et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Differential gene expression profile in monocytic myeloid‐derived suppressor cells at maternal–fetal interface in a mouse model of spontaneous abortion

Ren

Zeng

Tian

et al. 2018

Journal Cellular Physiology

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Background Monocytic myeloid‐derived suppressor cells (MO‐MDSCs) play an important role in maintaining normal pregnancy. However, it is still not clear what kind of changes in MO‐MDSCs may lead to miscarriage, and which gene expression changes take place when MO‐MDSCs migrate to the uterus as bone marrow‐derived cells. Methods We used flow sorting technology to obtain MO‐MDSCs from the maternal–fetal interface and bone marrow, respectively. Affymetrix 3′IVT expression profiling chip technology was used to detect the differential gene expression profiles in MO‐MDSCs at the maternal–fetal interface in a mouse model of spontaneous abortion compared with the normal fertility control mice. We also compared the differential gene expression of MO‐MDSCs at the maternal–fetal interface compared with bone marrow in the normal fertility control mice. Results We found that 3,409 genes in MO‐MDSCs were upregulated and 1,539 genes were downregulated at the maternal–fetal interface in the spontaneous abortion mice compared with the normal fertility mice. These genes are enriched in cellular components, biological processes, molecular functions, and protein binding, tumor signaling pathway, the PI3K–Akt signaling pathway, intratumoral proteoglycans, and extracellular matrix receptor interactions. Furthermore, we found that 270 genes in MO‐MDSCs were upregulated and 383 genes were downregulated at the maternal–fetal interface in the normal fertility mice compared with those in the bone marrow. These genes are enriched in cellular components, biological processes, molecular functions, cell cycle, tumor transcriptional disorder, and cell adhesion molecules. Conclusion Differential gene expression in MO‐MDSCs likely contributes to a successful pregnancy in fetal–maternal immunotolerance.

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Section: Introductionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Differential gene expression profile in monocytic myeloid‐derived suppressor cells at maternal–fetal interface in a mouse model of spontaneous abortion

Ren

Zeng

Tian

et al. 2018

Journal Cellular Physiology

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“…Similar results were also confirmed by functional MDSCs transfer transplantation model [21]. In terms of mechanisms, it has been reported that TGF-β played a central role in MDSCs mediated Tregs induction [93]. In addition to Tregs induction from CD4 + /CD25 − T cells, MDSCs derived TGF-β also offered Tregs plasticity that Th17 cells transdifferentiated into Foxp3 + Tregs [94].…”

Section: Relationships Between Mdscs and Other Immune Cellssupporting

confidence: 65%

Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation

Nakamura

Ushigome

2018

IJMS

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Regulation of allo-immune responses is proposed as a topic for investigation in the current field of organ transplantation. As a regulator, regulatory T cells (Tregs) have received attention due to their ability to control allograft rejection. Concurrently, however, the independent action of Tregs is not enough to achieve tolerance status in many situations. Meanwhile, as a multi-functional regulator, myeloid-derived suppressor cells (MDSCs) can suppress effector T cells as well as induce Tregs or regulatory B cells (Bregs) in certain circumstances. Furthermore, the importance of a crosstalk between MDSCs and natural killer T cells to induce tolerance has been reported. Thus, orchestration between MDSCs, myeloid regulators, T/Bregs and other lymphoid/myeloid regulators can shed light on achieving allogeneic tolerance. Here, we review the current knowledge in terms of immunological regulatory function displayed by MDSCs in the context of organ transplantation. Ideal control of MDSCs would lead to a reduction of allograft rejection and subsequent long-term allograft acceptance.

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“…Before birth, GR-MDSC may play a critical role in maintaining maternal-fetal tolerance [12,13,34,35], being beneficial for fetal life, whereas postnatally elevated GR-MDSC numbers may contribute to postnatal immunosuppression and susceptibility to infections. Before birth, GR-MDSC may play a critical role in maintaining maternal-fetal tolerance [12,13,34,35], being beneficial for fetal life, whereas postnatally elevated GR-MDSC numbers may contribute to postnatal immunosuppression and susceptibility to infections.…”

Section: Gr-mdsc In Preterm Infantsmentioning

confidence: 99%

Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period

Schwarz

Scheckenbach

Kugel

et al. 2017

Clinical and Experimental Immunology

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Preterm delivery is the leading cause of perinatal morbidity and mortality. Among the most important complications in preterm infants are peri- or postnatal infections. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells. Emerging evidence suggests that granulocytic MDSC (GR-MDSC) play a pivotal role in mediating maternal-fetal tolerance. The role of MDSC for postnatal immune-regulation in neonates is incompletely understood. Until the present time, nothing was known about expression of MDSC in preterm infants. In the present pilot study, we quantified GR-MDSC counts in cord blood and peripheral blood of preterm infants born between 23 + 0 and 36 + 6 weeks of gestation (WOG) during the first 3 months of life and analysed the effect of perinatal infections. We show that GR-MDSC are increased in cord blood independent of gestational age and remain elevated in peripheral blood of preterm infants during the neonatal period. After day 28 they drop to nearly adult levels. In case of perinatal or postnatal infection, GR-MDSC accumulate further and correlate with inflammatory markers C-reactive protein (CRP) and white blood cell counts (WBC). Our results point towards a role of GR-MDSC for immune-regulation in preterm infants and render them as a potential target for cell-based therapy of infections in these patients.

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Granulocytic myeloid-derived suppressor cells maintain feto-maternal tolerance by inducing Foxp3 expression in CD4⁺CD25⁻T cells by activation of the TGF-β/β-catenin pathway

Abstract: This research was supported by the National Natural Science Foundation of China (Grant No. 81270715; 91442113). The authors have nothing to disclose.

Cited by 66 publications

References 48 publications

Differential gene expression profile in monocytic myeloid‐derived suppressor cells at maternal–fetal interface in a mouse model of spontaneous abortion

Differential gene expression profile in monocytic myeloid‐derived suppressor cells at maternal–fetal interface in a mouse model of spontaneous abortion

Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation

Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period

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Granulocytic myeloid-derived suppressor cells maintain feto-maternal tolerance by inducing Foxp3 expression in CD4+CD25−T cells by activation of the TGF-β/β-catenin pathway

Abstract: This research was supported by the National Natural Science Foundation of China (Grant No. 81270715; 91442113). The authors have nothing to disclose.

Cited by 66 publications

References 48 publications

Differential gene expression profile in monocytic myeloid‐derived suppressor cells at maternal–fetal interface in a mouse model of spontaneous abortion

Differential gene expression profile in monocytic myeloid‐derived suppressor cells at maternal–fetal interface in a mouse model of spontaneous abortion

Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation

Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period

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Granulocytic myeloid-derived suppressor cells maintain feto-maternal tolerance by inducing Foxp3 expression in CD4⁺CD25⁻T cells by activation of the TGF-β/β-catenin pathway