Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

Zhang, Yun; Qu, Daiwei; Sun, Jia; Zhao, Lei; Wang, Qingjie; Shao, Qianqian; Kong, Beihua; Qu, Xun

doi:10.1038/cmi.2015.41

Cited by 39 publications

(26 citation statements)

References 38 publications

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“…CCR2 is the membranous receptor for C-C motif chemokine 2 (CCL2), and the CCR2-CCL2 signaling axis plays important roles in mediating monocyte migration and the progression of numerous inflammatory diseases. [34][35][36] Using CCR2, we successfully divided decidual macrophages into two subsets (Fig. 1e).…”

Section: Resultsmentioning

confidence: 99%

Three macrophage subsets are identified in the uterus during early human pregnancy

Jiang

et al. 2018

Cell Mol Immunol

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Macrophages are crucial for a successful pregnancy, and malfunctions of decidual macrophages correlate with adverse pregnancy outcomes, such as spontaneous abortion and preeclampsia. Previously, decidual macrophages were often thought to be a single population. In the present study, we identified three decidual macrophage subsets, CCR2-CD11cLO (CD11c, ~80%), CCR2-CD11cHI (CD11c, ~5%), and CCR2+CD11cHI (CD11c, 10-15%), during the first trimester of human pregnancy by flow cytometry analysis. CCR2-CD11cLO macrophages are widely distributed in the decidua, while CCR2-CD11cHI and CCR2+CD11cHI macrophages are primarily detected close to extravillous trophoblast cells according to immunofluorescence staining. According to RNA sequencing bioinformatics analysis and in vitro functional studies, these three subsets of macrophages have different phagocytic capacities. CCR2+CD11cHI macrophages have pro-inflammatory characteristics, while the CCR2-CD11cHI population is suggested to be anti-oxidative and anti-inflammatory due to its high expression of critical heme metabolism-related genes, suggesting that these two subsets of macrophages maintain an inflammatory balance at the leading edge of trophoblast invasion to facilitate the clearance of pathogen infection as well as maintain the homeostasis of the maternal-fetal interface. The present study physiologically identifies three decidual macrophage subsets. Further clarification of the functions of these subsets will improve our understanding of maternal-fetal crosstalk in the maintenance of a healthy pregnancy.

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Section: Resultsmentioning

confidence: 99%

Three macrophage subsets are identified in the uterus during early human pregnancy

Jiang

et al. 2018

Cell Mol Immunol

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“…In an in vitro coculture system, CCL2 secreted from the trophoblast cell line HTR8/SVneo was shown to mediate the differentiation of CD14+ myelomonocytic cells into CD14+HLA-DR(-/low) MDSCs, as addition of anti-CCL2 antibody markedly reduced CD14 expression compared to untreated and isotype-control-treated cells. The effect on differentiation occurred at least partly in a STAT3-dependent manner (161). Another study by Fujisaka et al indirectly implies an effect of CCL2 on MDSC differentiation.…”

Section: Ccl2 Impacts Myeloid Cell Maturation and Differentiationmentioning

confidence: 98%

More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis

2019

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Monocyte chemoattractant protein-1 (MCP-1/CCL2) is renowned for its ability to drive the chemotaxis of myeloid and lymphoid cells. It orchestrates the migration of these cell types both during physiological immune defense and in pathological circumstances, such as autoimmune diseases including rheumatoid arthritis and multiple sclerosis, inflammatory diseases including atherosclerosis, as well as infectious diseases, obesity, diabetes, and various types of cancer. However, new data suggest that the scope of CCL2's functions may extend beyond its original characterization as a chemoattractant. Emerging evidence shows that it can impact leukocyte behavior, influencing adhesion, polarization, effector molecule secretion, autophagy, killing, and survival. The direction of these CCL2-induced responses is context dependent and, in some cases, synergistic with other inflammatory stimuli. The involvement of CCL2 signaling in multiple diseases renders it an interesting therapeutic target, although current targeting strategies have not met early expectations in the clinic. A better understanding of how CCL2 affects immune cells will be pivotal to the improvement of existing therapeutic approaches and the development of new drugs. Here, we provide an overview of the pleiotropic effects of CCL2 signaling on cells of the myeloid lineage, beyond chemotaxis, and highlight how these actions might help to shape immune cell behavior and tumor immunity.

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“…These results indicated that abortion may be caused by the imbalance of local immune cells and immune molecules, but does not involve the central hematopoietic system. However, chemokines and chemokine receptors expressed by cells in the maternal‐fetal microenvironment may also affect the amount of localized MDSCs . MDSCs can produce immunosuppressive effects in the local microenvironment by secreting immunosuppressive molecules (especially ARG‐1, iNOS, IL‐10, and TGF‐β), and their homeostasis is the key to maintaining immune tolerance .…”

Section: Discussionmentioning

confidence: 99%

Myeloid‐derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells

Ren

Zeng

Tian

et al. 2019

American J Rep Immunol

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Problem: Maternal immune system tolerance to the semiallogeneic fetus is critical for a successful pregnancy. Studies have shown that myeloid-derived suppressor cells (MDSCs) play an important role in maintaining feto-maternal tolerance. However, the mechanisms remain poorly understood. Methods: Flow cytometry was used to evaluate the percentage of MDSCs in an allogeneic-normal-pregnant mouse model during different periods of gestation. We further assessed the percentage of MDSCs and their subtypes (granulocytic MDSCs [GR-MDSCs] and monocytic MDSCs [MO-MDSCs]) in a spontaneous abortion mouse model. The levels of the immunosuppressive molecules ARG-1, iNOS, IL-10, and TGF-β in MDSCs were also evaluated. MDSCs were depleted by anti-Gr-1 injection, and the resorption rate was calculated. The cytotoxicity of decidual natural killer (NK) cells was evaluated, and the percentage of regulatory NK (NKreg) cells and regulatory T lymphocytes (Tregs) were evaluated. Results: Myeloid-derived suppressor cells was accumulated in a time-dependent manner during pregnancy. However, the percentage of MDSCs was decreased in the spontaneous abortion mice compared with that in the control mice. In addition, the levels of ARG-1, iNOS, IL-10, and TGF-β in MDSCs decreased differentially. Finally, depletion of MDSCs was associated with increased rates of resorption and the proportion of NKreg and Treg cells in uterine tissues; meanwhile, the cytotoxicity of decidual NK cells was upregulated by increasing the level of perforin, granzyme B, and natural killer group protein 2 D-activating NK receptor (NKG2D). Conclusion: Depletion of MDSCs may cause pregnancy loss, while upregulating the cytotoxicity of decidual NK cells and increasing NKreg and Treg cell numbers. K E Y W O R D S cytotoxicity, decidual natural killer cells, myeloid-derived suppressor cells, pregnancy loss, regulatory NK cells, regulatory T lymphocytes How to cite this article: Ren J, Zeng W, Tian F, et al. Myeloidderived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells. Am

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Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

Cited by 39 publications

References 38 publications

Three macrophage subsets are identified in the uterus during early human pregnancy

Three macrophage subsets are identified in the uterus during early human pregnancy

More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis

Myeloid‐derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells

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