scholarly journals Characterization of dendritic cell (DC)-10 in recurrent miscarriage and recurrent implantation failure

Reproduction ◽  
2019 ◽  
Vol 158 (3) ◽  
pp. 247-255
Author(s):  
Su Liu ◽  
Hongxia Wei ◽  
Yuye Li ◽  
Lianghui Diao ◽  
Ruochun Lian ◽  
...  

During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions toward tolerance rather than active immune response. IL-10 plays a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from ten normal fertile controls, six RM women and seven RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.

Author(s):  
Forough Parhizkar ◽  
Roza Motavalli-Khiavi ◽  
Leili Aghebati-Maleki ◽  
Zahra Parhizkar ◽  
Ramin Pourakbari ◽  
...  

2021 ◽  
Vol 22 (6) ◽  
pp. 3021
Author(s):  
Jeong Yong Lee ◽  
Eun Hee Ahn ◽  
Hyeon Woo Park ◽  
Ji Hyang Kim ◽  
Young Ran Kim ◽  
...  

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization–embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.


2010 ◽  
Vol 93 (2) ◽  
pp. 437-441 ◽  
Author(s):  
Erika B. Johnston-MacAnanny ◽  
Janice Hartnett ◽  
Lawrence L. Engmann ◽  
John C. Nulsen ◽  
M. Melinda Sanders ◽  
...  

2011 ◽  
Vol 79 (8) ◽  
pp. 3046-3052 ◽  
Author(s):  
Isabel Dellacasa-Lindberg ◽  
Jonas M. Fuks ◽  
Romanico B. G. Arrighi ◽  
Henrik Lambert ◽  
Robert P. A. Wallin ◽  
...  

ABSTRACTDisseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome. Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescentToxoplasmainfection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasitesin situin the brain parenchyma.Toxoplasma gondiitachyzoites were allowed to infect primary microglia and astrocytesin vitro. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia,Toxoplasma-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. YetToxoplasma-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cellsin vitro. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as “Trojan horses,” paradoxically facilitating dissemination ofToxoplasmawithin the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.


2017 ◽  
Vol 107 (1) ◽  
pp. 136-143.e2 ◽  
Author(s):  
Yihua Yang ◽  
Xiaoyan Chen ◽  
Sotirios H. Saravelos ◽  
Yingyu Liu ◽  
Jin Huang ◽  
...  

2021 ◽  
Author(s):  
Shijian Lv ◽  
Mei Liu ◽  
Lizhen Xu ◽  
Cong Zhang

Abstract Background: Recurrent miscarriage (RM) is a very frustrating problem for both couples and clinicians. To date, the etiology of RM remains poorly understood. Decidualization plays a critical role in implantation and the maintenance of pregnancy, and its deficiency is closely correlated with RM. The F-box protein S-phase kinase associated protein 2 (SKP2) is a key component of the SCF-type E3 ubiquitin ligase complex, which is critically involved in ErbB family-induced Akt ubiquitination, aerobic glycolysis and tumorigenesis. SKP2 is pivotal for reproduction, and SKP2-deficient mice show impaired ovarian development and reduced fertility.Methods: Here, we investigated the expression and function of SKP2 in human decidualization and its relation with RM. A total of 40 decidual samples were collected. Quantitative PCR analysis, western blot analysis and immunohistochemistry analysis were performed to analyze the differential expression of SKP2 between RM and control cells. For in vitro induction of decidualization, both HESCs (human endometrial stromal cells) cell line and primary ESCs (endometrial stromal cells) were used to analyze the effects of SKP2 on decidualization via siRNA transfection.Results: Compared to normal pregnant women, the expression of SKP2 was reduced in the decidual tissues from individuals with RM. After in vitro induction of decidualization, knockdown of SKP2 apparently attenuated the decidualization of HESCs and resulted in the downregulation of HOXA10 and FOXM1, which are essential for normal human decidualization. Moreover, our experiments demonstrated that SKP2 silencing reduced the expression of its downstream target GLUT1.Conclusions: Our study indicates a functional role of SKP2 in RM: downregulation of SKP2 in RM leads to impaired decidualization and downregulation of GLUT1 and consequently predisposes individuals to RM.


2021 ◽  
Author(s):  
Mi Han ◽  
Yi Cao ◽  
Wenjie Zhou ◽  
Mingjuan Zhou ◽  
Xiaowei Zhou ◽  
...  

Abstract Impaired endometrial receptivity is the main cause of recurrent implantation failure (RIF), however, its underlying mechanism is unclear. In this study, we found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility who successfully achieved conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to those in the control group (P = 0.001), consistent with the results of genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells cause marked deficiency in supporting blastocysts and human embryonic JAR cell adhesion, mimicking the process of embryo adhesion. However, overexpression of HMGB1 had no effect on cell proliferation and in-vitro decidualization in a human endometrial stromal cell line (T-HESCs) and in primary human endometrial stromal cells (HESCs). These findings indicate that increased HMGB1 levels suppressed the adhesion capability of epithelial cells, contributing to impaired endometrial receptivity in patients with recurrent implantation failure. This characteristic can be used as a target for detecting and treating recurrent implantation failure in clinical practice.


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