Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+ regulatory T-cell and killer cell immunoglobulin-like receptor levels

Quan, Xiaozhen; Yang, Xuezhou

doi:10.3892/etm.2017.4634

Cited by 10 publications

(3 citation statements)

References 16 publications

(17 reference statements)

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“…In pathogen‐induced miscarriage animal model, Foxp3 expression is inhibited in peripheral blood, inguinal lymph nodes, and spleen as well as at the maternal‐foetal interface . In spontaneous abortion patients, Foxp3 expression are dramatically reduced in CD4 + CD25 + T cells in peripheral blood . Our study indicated that Foxp3 expression is suppressed in peripheral blood as well as placenta from FGR patients.…”

Section: Discussionmentioning

confidence: 60%

Dysfunction of Tregs contributes to FGR pathogenesis via regulating Smads signalling pathway

Wang

et al. 2020

J Cellular Molecular Medi

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Fetal growth restriction (FGR) is ranked number two of most common complication of abnormal pregnancy worldwide. The pathogenesis of FGR is complicated due to multiple aetiologies and the exact mechanism for FGR development is currently unknown. T regulatory cells (Tregs) are proven to play central roles in the maintenance of normal pregnancy. Peripheral blood samples of 102 pregnant human were collected analysed using flow cytometry to identify Tregs. We found that reduced Tregs and down‐regulation of Foxp3 were observed in peripheral blood of FGR patients. In FGR mouse model, we have found that Tregs were not only reduced in spleen but also in placenta. In vitro, Foxp3 and its transcription regulatory signalling molecules, including P‐Smad2, P‐Smad3 and Smad4, were diminished as well. Inhibition on Foxp3 expression was partially reversed by overexpression of Smad2 and Smad4. In FGR patients, Western blot results revealed that Foxp3, P‐Smad2, P‐Smad3 and Smad4 expression was inhibited in placenta. Our preliminary result suggests that maternal‐foetal immune tolerance mediated by Tregs plays an essential role in the development of FGR. The inhibited expression of Foxp3 and down‐regulated Smad2/Smad3/Smad4 signalling pathway were involved in the FGR pathogenesis. Targeting maternal‐foetal immune tolerance through Tregs might represent a novel therapeutic option for FGR.

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Section: Discussionmentioning

confidence: 60%

Dysfunction of Tregs contributes to FGR pathogenesis via regulating Smads signalling pathway

Wang

et al. 2020

J Cellular Molecular Medi

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“…Qian et al [50] reported that the proportion of peripheral CD4 + CD25 + CD127 low Tregs was not higher in pregnant women with a history of URSA than in nonpregnant women with URSA, whereas the percentage of Tregs, the expression level of CTLA-4 in CD4 + CD25 + CD127 low cells, and the proportion of CD4 + FOXP3 + cells in the decidua were significantly lower in patients with URSA than in normal controls. On the other hand, Quan et al [51] reported no differences in the percentages of peripheral CD4 + CD25 + cells among total CD4 + cells or FOXP3 + cells among CD4 + CD25 + cells between nonpregnant URSA patients, early-term URSA patients, normal women who underwent planned abortions, and normal nonpregnant controls. These studies used different antibody panels to identify Tregs at various phases of the menstrual cycle [18]; both these factors are likely to have affected the proportions of Tregs observed.…”

Section: Discussionmentioning

confidence: 98%

Reduced frequency and functional defects of CD4+CD25highCD127low/− regulatory T cells in patients with unexplained recurrent spontaneous abortion

Luo

Zeng

Huang

et al. 2020

Reprod Biol Endocrinol

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Background Unexplained recurrent spontaneous abortion (URSA) is defined as two or more consecutive pregnancy losses, generally of unknown cause; it is related to a failure of fetal–maternal immunological tolerance. Regulatory T cells (Tregs) exert immunosuppressive effects, which are essential to maintain fetal–maternal immunological tolerance and regulate immune balance. In this study, we used the specific cell-surface phenotype of CD4+CD25highCD127low/− Tregs to investigate the number and suppressive function of Tregs isolated from the peripheral blood of patients with URSA with the aim of expanding our understanding of their role in URSA. Methods We isolated a relatively pure population of peripheral CD4+CD25highCD127low/− Tregs and CD4+CD25− responder T cells (Tresps) from the patients with URSA and normal fertile nonpregnant control women via fluorescence-activated cell sorting. We compared the frequency, suppressive capacity, and forkhead box transcription factor P3 (FOXP3) expression of Tregs in the peripheral blood between patients with URSA and normal controls. Results The frequency of CD4+CD25highCD127low/− Tregs in the peripheral blood was lower in URSA patients than in the controls (P < 0.05). The mean fluorescence intensity of FOXP3 and FOXP3 mRNA expression in Tregs was also significantly lower in the URSA patients (P < 0.01). Tregs suppressed the activity of autologous Tresps stimulated with anti-CD3/CD28 beads in a concentration-dependent manner, with the strongest suppression occurring in cocultures with a 1:1 Treg:Tresp ratio in both groups; however, patient-derived Tregs exhibited a poorer capacity to suppress the proliferation of autologous Tresps than the Tregs from normal controls (P < 0.01). Moreover, Tregs isolated from URSA patients inhibited the proliferation of Tresps from normal controls less potently than the Tregs from normal controls (P < 0.01), and Tresps from URSA patients were less effectively suppressed by autologous Tregs than by those from normal controls (P < 0.01). Tresp activity were intact in both groups. Conclusions We observed a lower frequency of peripheral CD4+CD25highCD127low/− Tregs with lower FOXP3 expression in the peripheral blood of URSA patients. In addition, highly purified Tregs from patients with URSA exhibited impaired suppressive effects. The defect in immune regulation in URSA patients appears to be primarily related to impaired Tregs, and not to increased resistance of Tresps to suppression. Our findings reveal a potential novel therapeutic target for URSA.

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“…Without a delicate maternal-fetal immune balance, a series of pregnancy-related complications will occur, such as spontaneous abortion, preterm birth, and pre-eclampsia. Functional differentiation of T cells, especially the effect of cytokines on URPL, has been one of the focuses of immunological research in recent years [ 19 ]. An imbalance in Th17/Treg cells may be involved in autoimmune, inflammatory, and allergic conditions and pregnancy-related complications.…”

Section: Discussionmentioning

confidence: 99%

Regulatory effect of daphnetin on the balance of Th17 and Treg cells in the peripheral blood mononuclear cells from patients with unexplained recurrent pregnancy loss

Zhang

Long

Huang

et al. 2020

cejoi

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Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+ regulatory T-cell and killer cell immunoglobulin-like receptor levels

Cited by 10 publications

References 16 publications

Dysfunction of Tregs contributes to FGR pathogenesis via regulating Smads signalling pathway

Dysfunction of Tregs contributes to FGR pathogenesis via regulating Smads signalling pathway

Reduced frequency and functional defects of CD4+CD25highCD127low/− regulatory T cells in patients with unexplained recurrent spontaneous abortion

Regulatory effect of daphnetin on the balance of Th17 and Treg cells in the peripheral blood mononuclear cells from patients with unexplained recurrent pregnancy loss

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