Elevated levels of dehydroepiandrosterone as a potential mechanism of dendritic cell impairment during pregnancy

Черных, Е. Р.; Леплина, О. Ю.; Тихонова, М. А.; Селедцова, Н. В.; Тыринова, Т. В.; Хонина, Н. А.; Останин, А. А.; Пасман, Н. М.

doi:10.1186/s12865-014-0065-9

Cited by 7 publications

(5 citation statements)

References 53 publications

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“…hASC and PBMC were isolated from fat tissue and venous blood of healthy donors ( n = 6 and n = 4, resp.). Donor hASC were cultured with activated T cells, which were isolated as a part of donor PBMC preparation (PBMC typically contain approximately 70% of T cells) [ 30 ]. To activate T cells, we used either phytohemagglutinin (PHA) or plate-bound anti-CD3 and anti-CD28 antibodies.…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1

Rubtsov

Goryunov

Romanov

et al. 2017

Stem Cells International

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Mesenchymal stromal cells (MSC) control excessive inflammation and create a microenvironment for tissue repair protecting from chronic inflammation and tissue fibrosis. We examined the molecular mechanisms of MSC immunomodulatory function in mixed cultures of human adipose-derived MSC with lymphocytes. Our data show that MSC promote unstimulated lymphocyte survival potentially by an increase in antigen presentation. Under inflammatory conditions, mimicked by stimulation of TCR in lymphocytes, MSC suppress activation and proliferation of stimulated T cells. Immunosuppression is accompanied by downregulation of IL-2Rα that negatively affects the survival of activated T cells. MSC upregulate transcription of indolamine-2,3-dioxygenase (IDO) and inducible NO synthase (iNOS), which generate products negatively affecting T cell function. Both MSC and lymphocytes dramatically increase the surface ICAM-1 level in mixed cultures. Antibody-mediated blockage of surface ICAM-1 partially releases MSC-mediated immune suppression in vitro. Our data suggest that MSC have cell-intrinsic molecular programs depending on the inflammatory microenvironment. We speculate that MSC sense soluble factors and respond by surface ICAM-1 upregulation. ICAM-1 is involved in the control of T cell activation leading to immunosuppression or modest stimulation depending on the T cell status. Immunomodulation by MSC ranging from support of naive T cell survival to immunosuppression of activated T cells may affect the tissue microenvironment protecting from aberrant regeneration.

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Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1

Rubtsov

Goryunov

Romanov

et al. 2017

Stem Cells International

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“…Chernykh et al . showed that DC impairment was found in patients with elevated DHEAS 58 . High levels of DHEAS could cause spontaneous abortions by causing abnormal immunization in pregnant women.…”

Section: Discussionmentioning

confidence: 95%

Novel high-coverage targeted metabolomics method (SWATHtoMRM) for exploring follicular fluid metabolome alterations in women with recurrent spontaneous abortion undergoing in vitro fertilization

Song

Wang

Guo

et al. 2019

Sci Rep

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The complexity of follicular fluid metabolome presents a significant challenge for qualitative and quantitative metabolite profiling, and for discovering the comprehensive biomarkers. In order to address this challenge, a novel SWATHtoMRM metabolomics method was used for providing broad coverage and excellent quantitative capability to discover the human follicular fluid metabolites related to recurrent spontaneous abortion (RSA) after in vitro fertilization and embryo transfer, and to evaluate their relationship with pregnancy outcome. The follicular fluid samples from the spontaneous abortion group (n = 22) and the control group (n = 22) were analyzed using ultra-performance liquid chromatography high-resolution mass spectrometry. A novel, high-coverage, targeted metabolomics method (SWATH to MRM) and a targeted metabolomics method were used to find and validate the differential metabolites between the two groups. A total of 18 follicular fluid metabolites, including amino acids, cholesterol, vitamins, fatty acids, cholic acid, lysophosphatidylcholine and other metabolites, were identified. In the RSA group, 8 metabolites, namely dehydroepiandrosterone, lysoPC(16:0), lysoPC(18:2), lysoPC(18:1), lysoPC(18:0), lysoPC(20:5), lysoPC(20:4), and lysoPC(20:3), were up-regulated, and 10 metabolites, namely phenylalanine, linoleate, oleic acid, docosahexaenoic acid, lithocholic acid, 25-hydroxyvitamin D3, hydroxycholesterol, 13-hydroxy-alpha-tocopherol, leucine, and tryptophan, were down-regulated. These differential metabolites related to RSA may provide a possible diagnostic basis and therapeutic target for RSA, as well as a scientific basis for elucidating the mechanism of RSA.

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“…CD274, as a B7 family member, plays an important role in inducing T cell activation and differentiation. Previous study showed that DCs from a normal pregnancy peripheral expressed a high level of CD274 compared to DCs in unpregnant women [ 31 ]. Our study further proved that DCs from RSA patients and RSA mice were characterized by decreased expression of CD274 compared with the NP group, which might contribute to an abnormal T cell activation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

The Role of Dendritic Cell Subsets in Recurrent Spontaneous Abortion and the Regulatory Effect of Baicalin on It

Lai

Hei

et al. 2022

Journal of Immunology Research

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Recurrent spontaneous abortion (RSA) is a relevant complication of pregnancy. Aberrant dendritic cell (DC) activities and differentiation have been identified to be involved in RSA, but the underlying mechanisms remain unclear. Baicalin from Radix Scutellariae possesses a wide range of pharmacological and biological activities. However, the effect of baicalin on DC function in RSA has not been investigated. Here, we analyzed the changes of peripheral and maternal-fetal interface DC subsets and function in patients and mice with RSA, respectively. Then, we further treated RSA mice with baicalin and analyzed the therapeutic effect and underlying mechanism. We found that DCs from the peripheral blood and decidua of RSA patients and the maternal-fetal of RSA mice were all polarized to conventional DCs, whose proportion was positively correlated with the mice embryo absorption rate. Moreover, DCs from RSA patients and mice showed increased expression of HLA-DR/MHC-II, CD80, and CD86 but decreased expression of CD274 and 33D1. Importantly, baicalin could alleviate embryo resorption of RSA mice by reversing conventional DCs to plasmacytoid DCs and functional molecule expression via inhibiting the STAT5-ID2 pathway. Our research further proved that DCs play an important role in the pathogenesis of RSA and baicalin might be used for treating RSA.

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Elevated levels of dehydroepiandrosterone as a potential mechanism of dendritic cell impairment during pregnancy

Cited by 7 publications

References 53 publications

Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1

Molecular Mechanisms of Immunomodulation Properties of Mesenchymal Stromal Cells: A New Insight into the Role of ICAM-1

Novel high-coverage targeted metabolomics method (SWATHtoMRM) for exploring follicular fluid metabolome alterations in women with recurrent spontaneous abortion undergoing in vitro fertilization

The Role of Dendritic Cell Subsets in Recurrent Spontaneous Abortion and the Regulatory Effect of Baicalin on It

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