Adoptive transfer of Tregs: A novel strategy for cell-based immunotherapy in spontaneous abortion: Lessons from experimental models

Mohammadi, Sasan; Abdollahi, Elham; Nezamnia, Maria; Esmaeili, Seyed‐Alireza; Tavasolian, Fataneh; Sathyapalan, Thozhukat; Sahebkar, Amirhossein

doi:10.1016/j.intimp.2020.107195

Cited by 20 publications

(19 citation statements)

References 109 publications

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“…Recent investigations in mouse models have indicated that adoptive transfer of Tregs can prevent pregnancy loss in these models by improving maternal tolerance. Hence, passive cell therapy by autologous Tregs could be a potential novel therapeutic approach for cellbased immunotherapy for women with repeated spontaneous abortion [42].…”

Section: Discussionmentioning

confidence: 99%

Decrease in Regulatory T-cells and Increase in T Helper 17 Cells in Women With Recurrent Spontaneous Abortion

Badiee

Ghafourian

Ghadiri

et al. 2021

Preprint

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BackgroundAppearance of improper immune responses against the fetus and/or inadequate immunoregulatory mechanisms during pregnancy may lead to recurrent spontaneous abortion (RSA). TH17 cells play a significant role in inducing inflammation, autoimmune disease, and acute transplant rejection, while regulatory T (Treg) cells moderate the function of immune system in order to retain homeostasis.MethodsThis case-control study was designed to evaluate TH17 as well as Treg cells in 25 women with RSA and 25 age-matched healthy non-pregnant women. Flow cytometric assay was performed using monoclonal antibodies to detect CD4+CD25+ Treg cells (CD25dim and CD25bright). FoxP3 and RORγt expressions were compared using real-time PCR, and pro-inflammatory and anti-inflammatory cytokines were measured by ELISA kits. Independent-samples T test was employed for statistical analysis. ResultsThe ratio of CD4+CD25bright T cells was remarkably lower in women with RSA (P<0.05), and CD4+CD25dim T cells did not show any significant difference among the groups (P>0.05). RORγt was up-regulated, and FoxP3 was down-regulated significantly in case group (P<0.05). The significant increase of IL-6 and IL-17 as well as the decrease of TGF-β was indicated in RSA group (P<0.05). Also, IL-10 did not vary among the groups (P>0.05). ConclusionThese remarks prove that the decrease in regulatory factors such as CD4+CD25bright T-cells, TGF-β and FoxP3 expression may disrupt immune tolerance and homeostasis during pregnancy. Also, the environment rich in RORγt, IL-6, and IL-17 suggests the detrimental role of TH17 cells, which may lead to fetal rejection.

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Section: Discussionmentioning

confidence: 99%

Decrease in Regulatory T-cells and Increase in T Helper 17 Cells in Women With Recurrent Spontaneous Abortion

Badiee

Ghafourian

Ghadiri

et al. 2021

Preprint

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“…Tregs, as noted previously, may reduce the severity of cardiovascular complications in COVID-19 patients. Therapeutic interventions for enhancing tolerance based on the adoptive transfer of Tregs are an effective strategy to treat Treg-mediated diseases, including autoimmunity, spontaneous abortion and, tissue transplantation [151] , [152] . This includes isolating in vivo differentiated Tregs, expanding Tregs ex vivo , or generating iTreg cells in vitro and subsequent transfer into the body [151] , [152] .…”

Section: The Potential Of Treg Therapy In Reducing Cardiovascular Com...mentioning

confidence: 99%

“…Therapeutic interventions for enhancing tolerance based on the adoptive transfer of Tregs are an effective strategy to treat Treg-mediated diseases, including autoimmunity, spontaneous abortion and, tissue transplantation [151] , [152] . This includes isolating in vivo differentiated Tregs, expanding Tregs ex vivo , or generating iTreg cells in vitro and subsequent transfer into the body [151] , [152] . This strategy could be used to treat cardiovascular complications caused by severe COVID-19 infection.…”

Section: The Potential Of Treg Therapy In Reducing Cardiovascular Com...mentioning

confidence: 99%

“…In addition, probable adverse effects of artificially reinforcing Tregs, including diminished immune surveillance against tumors, need to be considered. Another issue that needs attention is the appropriate dose and subsets of Tregs [152] . The critical challenges for utilizing Treg therapy in treating cardiovascular complications in severe COVID-19 are the diagnosis of Treg cell deficiency and determining the appropriate time of adoptive transfer of Tregs.…”

Section: The Potential Of Treg Therapy In Reducing Cardiovascular Com...mentioning

confidence: 99%

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The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19

Saghafi¹,

Rezaee²,

Momtazi‐Borojeni³

et al. 2022

Life Sciences

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The SARS coronavirus 2 (SARS CoV-2) causes Coronavirus Disease (COVID-19), is an emerging viral infection. SARS CoV-2 infects target cells by attaching to Angiotensin-Converting Enzyme (ACE2). SARS CoV-2 could cause cardiac damage in patients with severe COVID-19, as ACE2 is expressed in cardiac cells, including cardiomyocytes, pericytes, and fibroblasts, and coronavirus could directly infect these cells. Cardiovascular disorders are the most frequent comorbidity found in COVID-19 patients. Immune cells such as monocytes, macrophages, and T cells may produce inflammatory cytokines and chemokines that contribute to COVID-19 pathogenesis if their functions are uncontrolled. This causes a cytokine storm in COVID-19 patients, which has been associated with cardiac damage. Tregs are a subset of immune cells that regulate immune and inflammatory responses. Tregs suppress inflammation and improve cardiovascular function through a variety of mechanisms. This is an exciting research area to explore the cellular, molecular, and immunological mechanisms related to reducing risks of cardiovascular complications in severe COVID-19. This review evaluated whether Tregs can affect COVID-19-related cardiovascular complications, as well as the mechanisms through which Tregs act.

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“…Spontaneous abortion (SA) is noninduced embryonic or fetal death before 20 weeks of gestation ( 1 ). The incidence of SA has been rising in recent years and accounts for nearly 10% to 15% of the total number of pregnancies worldwide ( 1 , 2 ). A number of studies have shown that various factors induce SA, including fetal chromosomal abnormalities, advanced maternal age, previous early pregnancy loss, alcohol consumption, smoking, and cocaine use ( 3 ).…”

mentioning

confidence: 99%

Circ-CCNB1 Modulates Trophoblast Proliferation and Invasion in Spontaneous Abortion by Regulating miR-223/SIAH1 axis

et al. 2022

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Purpose Spontaneous abortion (SA) is a common disorder in early pregnancy. Circular RNAs (circRNAs) have been reported to exert important regulatory effects on trophoblast function and embryo development. The aim of this study was to explore whether and how circRNAs regulate trophoblast function in SA during early pregnancy. Methods Cell proliferation, 5-bromo-2-deoxyuridine (BrdU) staining, transwell, immunofluorescence, western blot, RNA pull-down and dual-luciferase reporter assays were performed to investigate the effect of circRNA cyclin B1 (circ-CCNB1) on trophoblast function in HTR-8/SVneo and JEG-3 cells. Results An in vitro study demonstrated that upregulation of circ-CCNB1 significantly inhibited trophoblast proliferation and invasion compared with the controls using HTR-8/SVneo and JEG-3 cells, respectively. Moreover, miR-223 was downregulated in the villous tissues of patients with SA and was further predicted and shown to negatively interact with circ-CCNB1, which is involved in trophoblast proliferation and invasion. Using bioinformatics tools and subsequent RNA pull-down and dual luciferase assays, we found that miR-223 directly targets seven in absentia homolog-1 (SIAH1) and that upregulation of miR-223 decreased circ-CCNB1-induced SIAH1 expression levels in HTR-8/SVneo cells. Interestingly, upregulation of circ-CCNB1 suppressed trophoblast proliferation and invasion through inhibition of CCNB1 nuclear translocation induced by SIAH1. Downregulation of SIAH1 enhanced circ-CCNB1-suppressed CCNB1 nuclear protein expression in trophoblast cells. Conclusions Circ-CCNB1 served as a modulator of trophoblast proliferation and invasion by sponging miR-223, thus forming a regulatory network of circ-CCNB1/miR-223/SIAH1 in modulating CCNB1 nuclear translocation, which enabled us to elucidate the molecular mechanisms involved in normal embryo implantation or in SA.

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Adoptive transfer of Tregs: A novel strategy for cell-based immunotherapy in spontaneous abortion: Lessons from experimental models

Cited by 20 publications

References 109 publications

Decrease in Regulatory T-cells and Increase in T Helper 17 Cells in Women With Recurrent Spontaneous Abortion

Decrease in Regulatory T-cells and Increase in T Helper 17 Cells in Women With Recurrent Spontaneous Abortion

The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19

Circ-CCNB1 Modulates Trophoblast Proliferation and Invasion in Spontaneous Abortion by Regulating miR-223/SIAH1 axis

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