Contribution of macrophages to fetomaternal immunological tolerance

Parasar, Parveen; Guru, N; Nayak, Nihar R.

doi:10.1016/j.humimm.2021.02.013

Cited by 25 publications

(27 citation statements)

References 85 publications

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“…Macrophages are one of the most important types of immune cells at the maternal-fetal interface [ 19 ]. An increasing number of studies have shown that EV miRNAs can induce polarization of macrophages in the tumor microenvironment [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent Miscarriage

Zhang

Tao

Cai

et al. 2022

Journal of Immunology Research

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Purpose. Numerous studies have described the presence of crosstalk between trophoblasts and macrophages and the critical role it plays in recurrent miscarriage (RM). However, the mechanism of trophoblast-derived extracellular vesicle (EV) miRNAs and their interactions with decidual macrophages in the pathogenesis of RM remains unclear. Materials and Methods. miRNA-seq was used to identify the differentially expressed miRNAs between RM patients and healthy controls. qPCR and in situ hybridization assays were performed to analyze the expression levels of miR-196a-5p in RM. THP-1 cells were treated with EVs, and qPCR and flow cytometry were performed to explore the polarization of macrophages. To explore the crosstalk between trophoblasts and macrophages, a coculture model and a series of cell function assays were performed. Results. We first demonstrated that miR-196a-5p expression was higher in the cytotrophoblasts of villous tissues and plasma EVs from RM patients. miR-196a-5p derived from trophoblasts could be transferred into macrophages via EVs to induce M1 polarization via IκBα-mediated NF-κB pathway. Moreover, we found that M1 macrophages induced by EV miR-196a-5p derived from trophoblasts conversely regulated the proliferation, migration, and apoptosis of trophoblasts via TNF-α. Conclusions. This study indicated that trophoblast-derived EV miR-196a-5p was positively associated with RM and functioned by regulating the crosstalk between trophoblasts and macrophages. These findings may attribute to identify a novel biomarker specific for RM.

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Section: Resultsmentioning

confidence: 99%

miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent Miscarriage

Zhang

Tao

Cai

et al. 2022

Journal of Immunology Research

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“…Our previous studies and other reports in mice have shown that VEGF directly regulates placental vascular development and functions and that excess VEGF signaling in the placenta interferes with normal placental vascular development [9,[13][14][15][16]. Targeted overexpression of VEGF in the maternal endometrium and targeted knockdown of sFlt1 in placental trophoblasts have both been shown to adversely affect the development of maternal vascular spaces, causing enlargement of maternal blood spaces, suggesting potential effects on TGC development and/or function [8,9].…”

Section: Introductionmentioning

confidence: 87%

“…Placental trophoblasts also express sFlt1, which plays an essential role in modulating the VEGF signal from the maternal endometrium [8,9,12,13]. Excess sFlt1 production during pregnancy in humans is associated with serious pregnancy complications, including preeclampsia, a major cause of maternal and fetal morbidity and death [8,9,[14][15][16]. Understanding the role of VEGF signaling in pregnancy therefore has implications for understanding not only placental development but also the pathogenesis of pregnancy complications.…”

Section: Introductionmentioning

confidence: 99%

VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions

et al. 2021

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Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts primarily on endothelial cells, but numerous studies suggest that VEGF also acts on non-endothelial cells, including trophoblast cells. Inhibition of VEGF signaling by excess production of the endogenous soluble VEGF receptor sFlt1 in trophoblast cells has been implicated in several pregnancy complications. Our previous studies and other reports have shown that VEGF directly regulates placental vascular development and functions and that excess VEGF production adversely affects placental vascular development. Trophoblast giant cells (TGCs) line the maternal side of the placental vasculature in mice and function like endothelial cells. In this study, we specifically examined the effect of excess VEGF signaling on TGC development associated with defective placental vascular development using two mouse models an endometrial VEGF overexpression model and a placenta-specific sFlt1 knockdown model. Placentas of endometrial VEGF-overexpressing dams at embryonic days (E) 11.5 and 14.5 showed dramatic enlargement of the venous maternal spaces in junctional zones. The size and number of the parietal TGCs that line these venous spaces in the placenta were also significantly increased. Although junctional zone venous blood spaces from control and VEGF-overexpressing dams were not markedly different in size at E17.5, the number and size of P-TGCs were both significantly increased in the placentas from VEGF-overexpressing dams. In sFlt1 knockdown placentas, however, there was a significant increase in the size of the sinusoidal TGC-lined, alkaline phosphatase-positive maternal blood spaces in the labyrinth. These results suggest that VEGF signaling plays an important role in maintaining the homeostasis of the maternal vascular space in the mouse placenta through modulation of TGC development and differentiation, similar to the effect of VEGF on endothelial cells in other vascular beds.

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“…There are thus major gaps in our mechanistic understanding of rejection in uterus transplant recipients, especially considering that T-cell and B-cell biology may be considerably altered by other immune subsets in the endometrium-such as macrophages and natural killer cells-that have unique phenotypes and functions in this anatomic location. 21,22 Finally, the consequences of smoldering or incompletely treated rejection on pregnancy outcomes are unknown. An improved understanding of the pathophysiology of rejection in UTx is greatly needed, as lessons learned from other organ transplant recipients may not be generalizable to this unique patient population.…”

Section: Rejectionmentioning

confidence: 99%

Immunologic and Infectious Concerns in Uterus Transplantation

Porrett¹,

Nellore

2021

Clinical Obstetrics &Amp; Gynecology

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Pharmacologic immunosuppression is required for the success of uterus transplantation but can provoke several complications for the transplant recipient. In this review, we discuss the immunologic complications that can occur in the uterus transplant recipient. First, we provide the latest update on immunosuppression regimens used by programs throughout the world. Next, we discuss the prevalence, mechanisms, treatment, and outcome of rejection in uterus transplant recipients. Finally, we discuss infectious complications of varying severity alongside their treatment and impact.

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Contribution of macrophages to fetomaternal immunological tolerance

Cited by 25 publications

References 85 publications

miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent Miscarriage

miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent Miscarriage

VEGF Maintains Maternal Vascular Space Homeostasis in the Mouse Placenta through Modulation of Trophoblast Giant Cell Functions

Immunologic and Infectious Concerns in Uterus Transplantation

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